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NM_000059.3(BRCA2):c.7879A>T (p.Ile2627Phe) AND Hereditary breast and ovarian cancer syndrome

Germline classification:
Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:
Aug 15, 2017
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:
RCV000045337.4

Allele description

NM_000059.3(BRCA2):c.7879A>T (p.Ile2627Phe)

Gene:
BRCA2:BRCA2, DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.3(BRCA2):c.7879A>T (p.Ile2627Phe)
HGVS:
  • NC_000013.11:g.32362596A>T
  • NG_012772.3:g.52117A>T
  • NM_000059.3:c.7879A>T
  • NP_000050.2:p.Ile2627Phe
  • LRG_293t1:c.7879A>T
  • LRG_293:g.52117A>T
  • LRG_293p1:p.Ile2627Phe
  • NC_000013.10:g.32936733A>T
  • U43746.1:n.8107A>T
  • p.I2627F
Nucleotide change:
8107A>T
Protein change:
I2627F
Links:
dbSNP: rs80359014
NCBI 1000 Genomes Browser:
rs80359014
Molecular consequence:
  • NM_000059.3:c.7879A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:
Hereditary breast and ovarian cancer
Identifiers:
MeSH: D061325; MedGen: C0677776; Orphanet: 145; OMIM: PS604370

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000073350Invitae
criteria provided, single submitter

(Nykamp K et al. (Genet Med 2017))
Likely pathogenic
(Aug 15, 2017)
germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

SCV000587918Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR)
no assertion criteria provided
Pathogenic
(Jan 31, 2014)
germlineresearch

SCV000592155Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Jul 29, 2016)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing, research
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel germline mutations in BRCA2 gene among breast and breast-ovarian cancer families from Poland.

Balabas A, Skasko E, Nowakowska D, Niwinska A, Blecharz P.

Fam Cancer. 2010 Sep;9(3):267-74. doi: 10.1007/s10689-010-9338-5.

PubMed [citation]
PMID:
20383589

Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer.

Couch FJ, Hart SN, Sharma P, Toland AE, Wang X, Miron P, Olson JE, Godwin AK, Pankratz VS, Olswold C, Slettedahl S, Hallberg E, Guidugli L, Davila JI, Beckmann MW, Janni W, Rack B, Ekici AB, Slamon DJ, Konstantopoulou I, Fostira F, Vratimos A, et al.

J Clin Oncol. 2015 Feb 1;33(4):304-11. doi: 10.1200/JCO.2014.57.1414. Epub 2014 Dec 1.

PubMed [citation]
PMID:
25452441
PMCID:
PMC4302212
See all PubMed Citations (13)

Details of each submission

From Invitae, SCV000073350.6

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

Description

This sequence change replaces isoleucine with phenylalanine at codon 2627 of the BRCA2 protein (p.Ile2627Phe). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals and families with breast and/or ovarian cancer (PMID: 10699917, 20104584, 21232165, 20383589, 25452441). It is also known as 8107A>T in the literature. ClinVar contains an entry for this variant (Variation ID: 52430). This variant is located in the DNA-binding domain (DBD) of the BRCA2 protein (PMID: 18451181). Experimental studies have shown that this variant affects BRCA2 homology-directed repair activity, regulation of centrosome amplification, and complementation of the lethality in BRCA2-deficient cells (PMID: 18451181, 23108138, 25146914). Multifactorial likelihood analyses based on genetic data using family history, co-segregation, and co-occurrence predict that this variant has a high probability of being deleterious (PMID: 17924331, 18451181, 21990134, 23108138). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

From Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR), SCV000587918.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearchnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000592155.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 30, 2018