NM_000059.4(BRCA2):c.3717del (p.Lys1239fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Dec 5, 2022
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:
RCV000132471.18

Allele description [Variation Report for NM_000059.4(BRCA2):c.3717del (p.Lys1239fs)]

NM_000059.4(BRCA2):c.3717del (p.Lys1239fs)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.4(BRCA2):c.3717del (p.Lys1239fs)
HGVS:
  • NC_000013.10:g.32912207del
  • NC_000013.11:g.32338072del
  • NG_012772.3:g.27593del
  • NM_000059.4:c.3717delMANE SELECT
  • NP_000050.3:p.Lys1239fs
  • LRG_293:g.27593del
  • NC_000013.10:g.32912207del
  • NC_000013.10:g.32912209del
  • NC_000013.10:g.32912209delA
  • NC_000013.11:g.32338072delA
  • NM_000059.3:c.3717delA
  • NM_000059.4:c.3717del
  • U43746.1:n.3945delA
  • p.K1239NFS*20
  • p.Lys1239Asnfs*20
Nucleotide change:
3945delA
Links:
Breast Cancer Information Core (BIC) (BRCA2): 3945&base_change=del A; dbSNP: rs80359401
NCBI 1000 Genomes Browser:
rs80359401
Molecular consequence:
  • NM_000059.4:c.3717del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000187565Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Oct 19, 2021) 		germlineclinical testing

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

Citation Link,

SCV000905010Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Dec 5, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Cancer variation associated with the position of the mutation in the BRCA2 gene.

Lubinski J, Phelan CM, Ghadirian P, Lynch HT, Garber J, Weber B, Tung N, Horsman D, Isaacs C, Monteiro AN, Sun P, Narod SA.

Fam Cancer. 2004;3(1):1-10.

PubMed [citation]
PMID:
15131399

Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years.

Malone KE, Daling JR, Doody DR, Hsu L, Bernstein L, Coates RJ, Marchbanks PA, Simon MS, McDonald JA, Norman SA, Strom BL, Burkman RT, Ursin G, Deapen D, Weiss LK, Folger S, Madeoy JJ, Friedrichsen DM, Suter NM, Humphrey MC, Spirtas R, Ostrander EA.

Cancer Res. 2006 Aug 15;66(16):8297-308.

PubMed [citation]
PMID:
16912212
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV000187565.8

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

Description

The c.3717delA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 3717, causing a translational frameshift with a predicted alternate stop codon (p.K1239Nfs*20). This mutation has been detected in multiple families with female breast cancer, male breast cancer, and/or ovarian cancer (Lubinski J et al. Fam. Cancer. 2004;3(1):1-10; Tchou J et al. Clin. Breast Cancer 2007 Jun;7:627-33; Tai YC et al. J. Natl. Cancer Inst. 2007 Dec 5;99(23):1811-4). Of note, this alteration is also designated as 3945delA in published literature. 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
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Color Diagnostics, LLC DBA Color Health, SCV000905010.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

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 detected in at least five individuals affected with breast cancer and in four suspected hereditary breast and ovarian cancer families (PMID: 15131399, 16912212, 17592676, 25673166, 33471991; Leiden Open Variation Database DB-ID BRCA2_004530; Color internal data). This variant has not been identified 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.

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

Last Updated: Oct 26, 2024