NM_000059.4(BRCA2):c.266C>T (p.Pro89Leu) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Nov 30, 2023
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:
RCV003230502.3

Allele description [Variation Report for NM_000059.4(BRCA2):c.266C>T (p.Pro89Leu)]

NM_000059.4(BRCA2):c.266C>T (p.Pro89Leu)

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.266C>T (p.Pro89Leu)
HGVS:
  • NC_000013.11:g.32319275C>T
  • NG_012772.3:g.8796C>T
  • NG_017006.2:g.1089G>A
  • NM_000059.4:c.266C>TMANE SELECT
  • NP_000050.2:p.Pro89Leu
  • NP_000050.3:p.Pro89Leu
  • LRG_293t1:c.266C>T
  • LRG_293:g.8796C>T
  • LRG_293p1:p.Pro89Leu
  • NC_000013.10:g.32893412C>T
  • NM_000059.3:c.266C>T
Protein change:
P89L
Links:
dbSNP: rs748609599
NCBI 1000 Genomes Browser:
rs748609599
Molecular consequence:
  • NM_000059.4:c.266C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

Name:
Breast-ovarian cancer, familial, susceptibility to, 2 (BROVCA2)
Synonyms:
Breast-ovarian cancer, familial 2
Identifiers:
MONDO: MONDO:0012933; MedGen: C2675520; Orphanet: 145; OMIM: 612555

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003926646KCCC/NGS Laboratory, Kuwait Cancer Control Center
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(May 30, 2023) 		unknownclinical testing

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

SCV004846754All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Nov 30, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown2not providednot provided108544not providedclinical testing
not providedunknownyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

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 KCCC/NGS Laboratory, Kuwait Cancer Control Center, SCV003926646.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedclinical testing PubMed (1)

Description

a variant of uncertain significance in the BRCA2 gene (p.Pro89Leu). This sequence change replaces proline, which is neutral and non polar, with leucine, which is neutral and non-polar, at codon 89 of the BRCA2 protein (p.Pro89Leu). This variant is present in population databases (rs748609599, gnomAD 0.006%). This missense change has been observed in individual(s) with a personal or family history of breast cancer, ovarian cancer, and/or pancreatic cancer (PMID: 21939546, 30199306, 31432501, 33067490). ClinVar contains an entry for this variant (Variation ID: 409565). In silico analysis supports that this missense variant does not alter protein structure/function. 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. Pathogenic variants in the BRCA2 gene are associated with hereditary breat/ovarian cancer syndrome.

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

From All of Us Research Program, National Institutes of Health, SCV004846754.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided2not providednot providednot provided

Last Updated: Nov 10, 2024