VCV000231854.34 - ClinVar - NCBI (2024)

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NM_024675.4(PALB2):c.466_467del (p.Ile156fs)

Germline

Classification Help

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(4) Help

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_024675.4(PALB2):c.466_467del (p.Ile156fs)

Variation ID: 231854 Accession: VCV000231854.34

Type and length

Deletion, 2 bp

Location

Cytogenetic: 16p12.2 16: 23636079-23636080 (GRCh38) [ NCBI UCSC ] 16: 23647400-23647401 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar
First in ClinVar Help

The date this variant first appeared in ClinVar with each type of classification.

Last submission Help

The date of the most recent submission for each type of classification for this variant.

Last evaluated Help

The most recent date that a submitter evaluated this variant for each type of classification.

Germline May 29, 2016 Jun 17, 2024 Dec 28, 2023
HGVS
Nucleotide Protein Molecular
consequence
NM_024675.4:c.466_467del MANESelect Help

Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.

NP_078951.2:p.Ile156fs frameshift
NM_024675.3:c.466_467delAT
NC_000016.10:g.23636080_23636081del
NC_000016.9:g.23647401_23647402del
NG_007406.1:g.10278_10279del
LRG_308:g.10278_10279del
LRG_308t1:c.466_467del LRG_308p1:p.Ile156fs
... more HGVS ... less HGVS
Protein change
I156fs
Other names
-
Canonical SPDI
NC_000016.10:23636078:ATA:A
Functional
consequence Help

The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

-

Global minor allele
frequency (GMAF) Help

The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

-

Allele frequency Help

The frequency of the allele represented by this VCV record.

-

Links
ClinGen: CA10580042
dbSNP: rs876659405
VarSome

Genes

Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation Viewer Help

Links to Variation Viewer, a genome browser to view variation data from NCBI databases.

Related variants
HI score Help

The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.

TS score Help

The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.

Within gene Help

The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.

All Help

The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.

PALB2 - - GRCh38
GRCh37
5856 5897

Conditions - Germline

Condition Help

The condition for this variant-condition (RCV) record in ClinVar.

Classification Help

The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses.


(# of submissions)
Review status Help

The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.

Last evaluated Help

The most recent date that a submitter evaluated this variant for the condition.

Variation/condition record Help

The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.

Hereditary cancer-predisposing syndrome

Pathogenic (1) Dec 28, 2023 RCV000214798.5

Familial cancer of breast

Pathogenic (2) Oct 13, 2023 RCV001045091.8

not provided

Likely pathogenic (1) Oct 1, 2019 RCV001091642.19

Submissions - Germline

Classification Help

The submitted germline classification for each SCV record.


(Last evaluated)
Review status Help

Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method.


(Assertion criteria)
Condition Help

The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.

Submitter Help

The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.

More information Help

This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.

Pathogenic

(Oct 13, 2023)

(Invitae Variant Classification Sherloc (09022015))

Method: clinical testing

Familial cancer of breast

Affected status: unknown

Allele origin: germline

Invitae

Accession: SCV001208921.5
First in ClinVar: Apr 15, 2020
Last updated: Feb 20, 2024

Publications:
PubMed (5)

PubMed: 1720066817200671172006722413693025099575

Comment:

This sequence change creates a premature translational stop signal (p.Ile156Phefs*11) in the PALB2 gene. It is expected to result in an absent or disrupted protein … (more)

This sequence change creates a premature translational stop signal (p.Ile156Phefs*11) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 231854). For these reasons, this variant has been classified as Pathogenic. (less)

Pathogenic

(Dec 28, 2023)

(Ambry Variant Classification Scheme 2023)

Method: clinical testing

Hereditary cancer-predisposing syndrome

Affected status: unknown

Allele origin: germline

Ambry Genetics

Accession: SCV000275831.7
First in ClinVar: May 29, 2016
Last updated: May 01, 2024

Comment:

The c.466_467delAT pathogenic mutation, located in coding exon 4 of the PALB2 gene, results from a deletion of two nucleotides at nucleotide positions 466 to … (more)

The c.466_467delAT pathogenic mutation, located in coding exon 4 of the PALB2 gene, results from a deletion of two nucleotides at nucleotide positions 466 to 467, causing a translational frameshift with a predicted alternate stop codon (p.I156Ffs*11). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)

Likely pathogenic

(Oct 01, 2019)

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Method: clinical testing

not provided

Affected status: yes

Allele origin: germline

CeGaT Center for Human Genetics Tuebingen

Accession: SCV001247810.22
First in ClinVar: May 12, 2020
Last updated: Jun 17, 2024

Number of individuals with the variant: 4

Pathogenic

(Sep 06, 2023)

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Method: clinical testing

Familial cancer of breast

Affected status: unknown

Allele origin: unknown

Myriad Genetics, Inc.

Accession: SCV004189418.1
First in ClinVar: Dec 24, 2023
Last updated: Dec 24, 2023

Comment:

This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

Comment:

This sequence change creates a premature translational stop signal (p.Ile156Phefs*11) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 231854). For these reasons, this variant has been classified as Pathogenic.

Comment:

The c.466_467delAT pathogenic mutation, located in coding exon 4 of the PALB2 gene, results from a deletion of two nucleotides at nucleotide positions 466 to 467, causing a translational frameshift with a predicted alternate stop codon (p.I156Ffs*11). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

Comment:

This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

This sequence change creates a premature translational stop signal (p.Ile156Phefs*11) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 231854). For these reasons, this variant has been classified as Pathogenic.

Comment:

The c.466_467delAT pathogenic mutation, located in coding exon 4 of the PALB2 gene, results from a deletion of two nucleotides at nucleotide positions 466 to 467, causing a translational frameshift with a predicted alternate stop codon (p.I156Ffs*11). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

Comment:

This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

Citations for germline classification of this variant

Help

Title Author Journal Year Link
Breast-cancer risk in families with mutations in PALB2. Antoniou AC The New England journal of medicine 2014 PMID: 25099575
The PALB2 gene is a strong candidate for clinical testing in BRCA1- and BRCA2-negative hereditary breast cancer. Janatova M Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2013 PMID: 24136930
Fanconi anemia is associated with a defect in the BRCA2 partner PALB2. Xia B Nature genetics 2007 PMID: 17200672
Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Reid S Nature genetics 2007 PMID: 17200671
PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Rahman N Nature genetics 2007 PMID: 17200668

Text-mined citations for rs876659405 ...

Help

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 17, 2024

Help

VCV000231854.34 - ClinVar - NCBI (2024)
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