U.S. flag

An official website of the United States government

NM_000059.4(BRCA2):c.7648A>G (p.Ile2550Val) AND Hereditary cancer-predisposing syndrome

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
May 4, 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:
RCV000776374.6

Allele description [Variation Report for NM_000059.4(BRCA2):c.7648A>G (p.Ile2550Val)]

NM_000059.4(BRCA2):c.7648A>G (p.Ile2550Val)

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.7648A>G (p.Ile2550Val)
HGVS:
  • NC_000013.11:g.32357772A>G
  • NG_012772.3:g.47293A>G
  • NM_000059.4:c.7648A>GMANE SELECT
  • NP_000050.2:p.Ile2550Val
  • NP_000050.3:p.Ile2550Val
  • LRG_293t1:c.7648A>G
  • LRG_293:g.47293A>G
  • LRG_293p1:p.Ile2550Val
  • NC_000013.10:g.32931909A>G
  • NM_000059.3:c.7648A>G
Protein change:
I2550V
Links:
dbSNP: rs41293507
NCBI 1000 Genomes Browser:
rs41293507
Molecular consequence:
  • NM_000059.4:c.7648A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000911806Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(May 4, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002670704Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Likely benign
(Jan 21, 2021) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium., Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]
PMID:
33471991
PMCID:
PMC7611105

Ovarian cancer risk of Chinese women with BRCA1/2 germline pathogenic variants.

Yao L, Sun J, Hu L, Chen J, Zhang J, Xu Y, Xie Y.

J Hum Genet. 2022 Nov;67(11):639-642. doi: 10.1038/s10038-022-01065-6. Epub 2022 Jul 21.

PubMed [citation]
PMID:
35864222
See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000911806.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This missense variant replaces isoleucine with valine at codon 2550 of the BRCA2 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: 35864222) and an unaffected individual (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_003369). This variant has been identified in 1/251108 chromosomes 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Ambry Genetics, SCV002670704.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Mar 30, 2024