NM_000059.4(BRCA2):c.7025_7026del (p.Gln2342fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 5, 2021
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:: RCV000574666.15

Allele description [Variation Report for NM_000059.4(BRCA2):c.7025_7026del (p.Gln2342fs)]

NM_000059.4(BRCA2):c.7025_7026del (p.Gln2342fs)

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.7025_7026del (p.Gln2342fs)

HGVS:

NC_000013.11:g.32354878_32354879del
NG_012772.3:g.44399_44400del
NM_000059.4:c.7025_7026delMANE SELECT
NP_000050.3:p.Gln2342fs
LRG_293:g.44399_44400del
NC_000013.10:g.32929015_32929016del
NM_000059.3:c.7025_7026delAA
U43746.1:n.7253_7254delAA
p.Gln2342Argfs*17

Nucleotide change:

7253delAA

Links:

Breast Cancer Information Core (BIC) (BRCA2): 7253&base_change=del AA; dbSNP: rs80359634

NCBI 1000 Genomes Browser:

rs80359634

Molecular consequence:

NM_000059.4:c.7025_7026del - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000661162	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 5, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 11400546, 20104584, 22160602, 31447099, 32125938, 9012404 Citation Link,
SCV000911870	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 15, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000661162

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 5, 2021)

germline

clinical testing

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

Citation Link,

SCV000911870

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 15, 2020)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

BRCA1/2 mutations in Swiss patients with familial or early-onset breast and ovarian cancer.

Schoumacher F, Glaus A, Mueller H, Eppenberger U, Bolliger B, Senn HJ.

Swiss Med Wkly. 2001 Apr 21;131(15-16):223-6.

PubMed [citation]

PMID:: 11400546

Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.

Borg A, Haile RW, Malone KE, Capanu M, Diep A, Törngren T, Teraoka S, Begg CB, Thomas DC, Concannon P, Mellemkjaer L, Bernstein L, Tellhed L, Xue S, Olson ER, Liang X, Dolle J, Børresen-Dale AL, Bernstein JL.

Hum Mutat. 2010 Mar;31(3):E1200-40. doi: 10.1002/humu.21202.

PubMed [citation]

PMID:: 20104584
PMCID:: PMC2928257

See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV000661162.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The c.7025_7026delAA pathogenic mutation, located in coding exon 13 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 7025 to 7026, causing a translational frameshift with a predicted alternate stop codon (p.Q2342Rfs*17). This mutation has been reported in both male and female breast cancer patients (Friedman LS et al. Am. J. Hum. Genet., 1997 Feb;60:313-9; Borg A et al. Hum Mutat, 2010 Mar;31:E1200-40; Schoumacher F et al. Swiss Med Wkly, 2001 Apr;131:223-6; Yadav S et al. J Clin Oncol, 2020 05;38:1409-1418; eMERGE Consortium et al. Am J Hum Genet, 2019 09;105:588-605; Schneegans SM et al. Fam Cancer, 2012 Jun;11:181-8). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Color Diagnostics, LLC DBA Color Health, SCV000911870.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant deletes 2 nucleotides in exon 14 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 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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