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NM_000059.4(BRCA2):c.3748G>A (p.Glu1250Lys) AND Hereditary breast ovarian cancer syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 28, 2020
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV001327561.7

Allele description [Variation Report for NM_000059.4(BRCA2):c.3748G>A (p.Glu1250Lys)]

NM_000059.4(BRCA2):c.3748G>A (p.Glu1250Lys)

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.3748G>A (p.Glu1250Lys)
HGVS:
  • NC_000013.11:g.32338103G>A
  • NG_012772.3:g.27624G>A
  • NM_000059.4:c.3748G>AMANE SELECT
  • NP_000050.2:p.Glu1250Lys
  • NP_000050.3:p.Glu1250Lys
  • LRG_293t1:c.3748G>A
  • LRG_293:g.27624G>A
  • LRG_293p1:p.Glu1250Lys
  • NC_000013.10:g.32912240G>A
  • NM_000059.3:c.3748G>A
Protein change:
E1250K
Links:
dbSNP: rs80358615
NCBI 1000 Genomes Browser:
rs80358615
Molecular consequence:
  • NM_000059.4:c.3748G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary breast ovarian cancer syndrome
Synonyms:
Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001518641Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 28, 2020) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001518641.4

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

Description

This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 230662). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 1250 of the BRCA2 protein (p.Glu1250Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine.

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

Last Updated: Sep 29, 2024