VCV004719034.1 - ClinVar

NM_024675.4(PALB2):c.3484G>C (p.Val1162Leu)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Uncertain significance
Uncertain significance (1)

This classification is based on the single submission received

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_024675.4(PALB2):c.3484G>C (p.Val1162Leu)

Variation ID: 4719034 Accession: VCV004719034.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16p12.2 16: 23603536 (GRCh38) [ NCBI UCSC ] 16: 23614857 (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	Feb 17, 2026	Feb 15, 2026	May 6, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_024675.4:c.3484G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_078951.2:p.Val1162Leu	missense
NM_001407296.1:c.3424G>C	NP_001394225.1:p.Val1142Leu	missense
NM_001407297.1:c.3412G>C	NP_001394226.1:p.Val1138Leu	missense
NM_001407298.1:c.3322G>C	NP_001394227.1:p.Val1108Leu	missense
NM_001407299.1:c.3247G>C	NP_001394228.1:p.Val1083Leu	missense
NM_001407300.1:c.3205G>C	NP_001394229.1:p.Val1069Leu	missense
NM_001407301.1:c.*119G>C		3 prime UTR
NM_001407302.1:c.*119G>C		3 prime UTR
NM_001407304.1:c.2599G>C	NP_001394233.1:p.Val867Leu	missense
NM_001407305.1:c.2599G>C	NP_001394234.1:p.Val867Leu	missense
NM_001407306.1:c.2599G>C	NP_001394235.1:p.Val867Leu	missense
NM_001407307.1:c.2437G>C	NP_001394236.1:p.Val813Leu	missense
NM_001407308.1:c.2362G>C	NP_001394237.1:p.Val788Leu	missense
NM_001407309.1:c.2362G>C	NP_001394238.1:p.Val788Leu	missense
NM_001407310.1:c.*119G>C		3 prime UTR
NM_001407311.1:c.*119G>C		3 prime UTR
NM_001407312.1:c.1696G>C	NP_001394241.1:p.Val566Leu	missense
NM_001407313.1:c.*119G>C		3 prime UTR
NM_001407314.1:c.1018G>C	NP_001394243.1:p.Val340Leu	missense
NC_000016.10:g.23603536C>G
NC_000016.9:g.23614857C>G
NG_007406.1:g.42822G>C
LRG_308:g.42822G>C
LRG_308t1:c.3484G>C	LRG_308p1:p.Val1162Leu

... more HGVS ... less HGVS

Protein change

V1142L, V566L, V788L, V867L, V1083L, V1108L, V813L, V1138L, V1069L, V1162L, V340L

Other names

Canonical SPDI

NC_000016.10:23603535:C:G

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

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
Gene	OMIM	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		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	6781	6829

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.
Familial cancer of breast	Uncertain significance (1)	criteria provided, single submitter	May 6, 2025	RCV006502229.1

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.	Expand all rows Collapse all rows 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.
Uncertain significance (May 06, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Familial cancer of breast	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV007384131.1 First in ClinVar: Feb 15, 2026 Last updated: Feb 15, 2026	Comment: show This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1162 of the PALB2 protein (p.Val1162Leu). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1162 of the PALB2 protein (p.Val1162Leu). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Apr 13, 2026