NM_024675.4(PALB2):c.968C>T (p.Ala323Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 29, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000564210.5

Allele description [Variation Report for NM_024675.4(PALB2):c.968C>T (p.Ala323Val)]

NM_024675.4(PALB2):c.968C>T (p.Ala323Val)

Gene:

PALB2:partner and localizer of BRCA2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_024675.4(PALB2):c.968C>T (p.Ala323Val)

HGVS:

NC_000016.10:g.23635578G>A
NG_007406.1:g.10780C>T
NM_024675.4:c.968C>TMANE SELECT
NP_078951.2:p.Ala323Val
NP_078951.2:p.Ala323Val
LRG_308t1:c.968C>T
LRG_308:g.10780C>T
LRG_308p1:p.Ala323Val
NC_000016.9:g.23646899G>A
NM_024675.3:c.968C>T

Protein change:

A323V

Links:

dbSNP: rs730881882

NCBI 1000 Genomes Browser:

rs730881882

Molecular consequence:

NM_024675.4:c.968C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

Clear Turn Off Turn On

3666 3890 3922 3986 5228 5241 5258 5264 5291 5343 5611 5612 5629 ... (16)
3666 3890 3922 3986 5228 5241 5258 5264 5291 5343 5611 5612 5629 5666 5818 6016[uid]
Search

GEO DataSets

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000666901	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 22, 2019)	germline	clinical testing	Citation Link,
SCV004357953	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 29, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31206626, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000666901

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 22, 2019)

germline

clinical testing

Citation Link,

SCV004357953

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 29, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Pathogenic and likely pathogenic variants in PALB2, CHEK2, and other known breast cancer susceptibility genes among 1054 BRCA-negative Hispanics with breast cancer.

Weitzel JN, Neuhausen SL, Adamson A, Tao S, Ricker C, Maoz A, Rosenblatt M, Nehoray B, Sand S, Steele L, Unzeitig G, Feldman N, Blanco AM, Hu D, Huntsman S, Castillo D, Haiman C, Slavin T, Ziv E.

Cancer. 2019 Aug 15;125(16):2829-2836. doi: 10.1002/cncr.32083. Epub 2019 Jun 17.

PubMed [citation]

PMID:: 31206626
PMCID:: PMC7376605

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Ambry Genetics, SCV000666901.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The p.A323V variant (also known as c.968C>T), located in coding exon 4 of the PALB2 gene, results from a C to T substitution at nucleotide position 968. The alanine at codon 323 is replaced by valine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Color Diagnostics, LLC DBA Color Health, SCV004357953.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This missense variant replaces alanine with valine at codon 323 of the PALB2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 31206626). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine