NM_000059.4(BRCA2):c.3814A>G (p.Met1272Val) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Feb 10, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV001703944.6

Allele description [Variation Report for NM_000059.4(BRCA2):c.3814A>G (p.Met1272Val)]

NM_000059.4(BRCA2):c.3814A>G (p.Met1272Val)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.3814A>G (p.Met1272Val)

Other names:

p.M1272V:ATG>GTG

HGVS:

NC_000013.11:g.32338169A>G
NG_012772.3:g.27690A>G
NM_000059.4:c.3814A>GMANE SELECT
NP_000050.2:p.Met1272Val
NP_000050.3:p.Met1272Val
LRG_293t1:c.3814A>G
LRG_293:g.27690A>G
LRG_293p1:p.Met1272Val
NC_000013.10:g.32912306A>G
NM_000059.3:c.3814A>G
U43746.1:n.4042A>G
p.M1272V

Nucleotide change:

4042A>G

Protein change:

M1272V

Links:

dbSNP: rs80358624

NCBI 1000 Genomes Browser:

rs80358624

Molecular consequence:

NM_000059.4:c.3814A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

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
SCV000210596	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Dec 19, 2018)	germline	clinical testing	Citation Link,
SCV002047251	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Feb 10, 2023)	unknown	clinical testing	PubMed (14) [See all records that cite these PMIDs] 17100994, 20104584, 14973102, 31825140, 32467295, 24817641, 31911673, 31214711, 30630528, 16949048, 28263838, 21520273, 30287823, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000210596

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(Dec 19, 2018)

germline

clinical testing

Citation Link,

SCV002047251

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Feb 10, 2023)

unknown

clinical testing

PubMed (14)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation analysis of BRCA1 and BRCA2 from 793 Korean patients with sporadic breast cancer.

Han SH, Lee KR, Lee DG, Kim BY, Lee KE, Chung WS.

Clin Genet. 2006 Dec;70(6):496-501.

PubMed [citation]

PMID:: 17100994

Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.

Borg A, Haile RW, Malone KE, Capanu M, Diep A, Törngren T, Teraoka S, Begg CB, Thomas DC, Concannon P, Mellemkjaer L, Bernstein L, Tellhed L, Xue S, Olson ER, Liang X, Dolle J, Børresen-Dale AL, Bernstein JL.

Hum Mutat. 2010 Mar;31(3):E1200-40. doi: 10.1002/humu.21202.

PubMed [citation]

PMID:: 20104584
PMCID:: PMC2928257

See all PubMed Citations (14)

Details of each submission

From GeneDx, SCV000210596.11

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

Description

This variant is associated with the following publications: (PMID: 17100994, 28263838, 21520273, 14973102, 20104584, 16949048, 24817641, 30287823, 31825140)

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002047251.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (14)

Description

The frequency of this variant in the general population, 0.0000089 (2/225816 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals affected with breast cancer (PMIDs: 14973102 (2004), 16949048 (2006), 17100994 (2006), 20104584 (2010), 30287823 (2018)) and prostate cancer (PMID: 31214711 (2020)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Additional analysis using software algorithms for the prediction of the effect of nucleotide changes on BRCA2 mRNA splicing yielded predictions that this variant may result in the gain of a cryptic splice site without affecting the natural splice sites . Based on the available information, we are unable to determine the clinical significance of this variant.

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

Last Updated: Dec 22, 2024

ClinVar

Relating variation to medicine