NM_000059.3(BRCA2):c.5631del (p.Asn1877fs) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Jan 15, 2020)

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:
RCV000166635.5

Allele description [Variation Report for NM_000059.3(BRCA2):c.5631del (p.Asn1877fs)]

NM_000059.3(BRCA2):c.5631del (p.Asn1877fs)

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.5631del (p.Asn1877fs)
HGVS:
  • NC_000013.11:g.32339986del
  • NG_012772.3:g.29507del
  • LRG_293t1:c.5631del
  • LRG_293:g.29507del
  • LRG_293p1:p.Asn1877fs
  • NC_000013.10:g.32914123del
  • NM_000059.3:c.5631delC
  • NM_000059.4:c.5631delCMANE SELECT
  • p.Asn1877Lysfs*32
  • p.N1877KFS*32
Nucleotide change:
5859delC
Links:
dbSNP: rs397507357
NCBI 1000 Genomes Browser:
rs397507357
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; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000217439Ambry Geneticscriteria provided, single submitter
Pathogenic
(Sep 27, 2018)
germlineclinical testing

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

Citation Link,

SCV000688935Color Health, Inccriteria provided, single submitter
Pathogenic
(Jan 15, 2020)
germlineclinical testing

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

Description

This variant deletes 1 nucleotide in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been identified in 1/248274 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

SCV000688935

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Recurrent BRCA1 and BRCA2 mutations in Mexican women with breast cancer.

Torres-Mejía G, Royer R, Llacuachaqui M, Akbari MR, Giuliano AR, Martínez-Matsushita L, Angeles-Llerenas A, Ortega-Olvera C, Ziv E, Lazcano-Ponce E, Phelan CM, Narod SA.

Cancer Epidemiol Biomarkers Prev. 2015 Mar;24(3):498-505. doi: 10.1158/1055-9965.EPI-13-0980. Epub 2014 Nov 4.

PubMed [citation]
PMID:
25371446
PMCID:
PMC4495576

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 Ambry Genetics, SCV000217439.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The c.5631delC pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 5631, causing a translational frameshift with a predicted alternate stop codon (p.N1877Kfs*32). In a study of 810 unselected women with breast cancer from Mexico, this mutation (designated as 5859delC) was identified in a 56-year-old female with DCIS (Torres-Mejía G et al. Cancer Epidemiol. Biomarkers Prev. 2015 Mar;24(3):498-505). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

From Color Health, Inc, SCV000688935.2

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

Last Updated: Sep 18, 2021

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