NM_000059.3(BRCA2):c.4127_4130del (p.Gly1376fs) AND not provided

Clinical significance:Pathogenic (Last evaluated: Sep 7, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000255023.2

Allele description [Variation Report for NM_000059.3(BRCA2):c.4127_4130del (p.Gly1376fs)]

NM_000059.3(BRCA2):c.4127_4130del (p.Gly1376fs)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.3(BRCA2):c.4127_4130del (p.Gly1376fs)
HGVS:
  • NC_000013.11:g.32338482_32338485del
  • NG_012772.3:g.28003_28006del
  • LRG_293t1:c.4127_4130del
  • LRG_293:g.28003_28006del
  • LRG_293p1:p.Gly1376fs
  • NC_000013.10:g.32912619_32912622del
  • NC_000013.10:g.32912619_32912622delGAAA
  • NM_000059.3:c.4127_4130delGAAA
  • p.Gly1376Alafs*11
Nucleotide change:
4355del4
Links:
dbSNP: rs397507323
NCBI 1000 Genomes Browser:
rs397507323

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000321458GeneDxcriteria provided, single submitter
Pathogenic
(Sep 7, 2018)
germlineclinical testing

Citation Link,

SCV000600575Quest Diagnostics Nichols Institute San Juan Capistranocriteria provided, single submitter
Pathogenic
(Dec 21, 2016)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Inherited predisposition to breast cancer among African American women.

Churpek JE, Walsh T, Zheng Y, Moton Z, Thornton AM, Lee MK, Casadei S, Watts A, Neistadt B, Churpek MM, Huo D, Zvosec C, Liu F, Niu Q, Marquez R, Zhang J, Fackenthal J, King MC, Olopade OI.

Breast Cancer Res Treat. 2015 Jan;149(1):31-9. doi: 10.1007/s10549-014-3195-0. Epub 2014 Nov 27.

PubMed [citation]
PMID:
25428789
PMCID:
PMC4298662

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

Details of each submission

From GeneDx, SCV000321458.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This deletion of 4 nucleotides in BRCA2 is denoted c.4127_4130delGAAA at the cDNA level and p.Gly1376AlafsX11 (G1376AfsX11) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GAGG[delGAAA]CACT. The deletion causes a frameshift, which changes a Glycine to an Alanine at codon 1376, and creates a premature stop codon at position 11 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.4127_4130delGAAA, previously reported as BRCA2 4355del4 using alternate nomenclature, has been observed in at least one individual with breast cancer (Churpek 2015). We consider this variant to be pathogenic.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000600575.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 10, 2021

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