NM_000059.4(BRCA2):c.6724_6725del (p.Asp2242fs) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 28, 2023
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:: RCV000758932.16

Allele description [Variation Report for NM_000059.4(BRCA2):c.6724_6725del (p.Asp2242fs)]

NM_000059.4(BRCA2):c.6724_6725del (p.Asp2242fs)

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.6724_6725del (p.Asp2242fs)

HGVS:

NC_000013.10:g.32915215_32915216del
NC_000013.11:g.32341079_32341080del
NG_012772.3:g.30600_30601del
NM_000059.4:c.6724_6725delMANE SELECT
NM_000059.4:c.6724_6725delGA
NP_000050.3:p.Asp2242fs
LRG_293:g.30600_30601del
NC_000013.10:g.32915215_32915216del
NC_000013.10:g.32915216_32915217del
NC_000013.10:g.32915216_32915217del
NC_000013.10:g.32915216_32915217delGA
NM_000059.3:c.6724_6725delGA
NM_000059.4:c.6724_6725del

Nucleotide change:

6952delGA

Links:

dbSNP: rs397507375

NCBI 1000 Genomes Browser:

rs397507375

Molecular consequence:

NM_000059.4:c.6724_6725del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000887886	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jun 29, 2018)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19656164, 26467025
SCV001779196	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 28, 2023)	germline	clinical testing	Citation Link,
SCV004565026	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Pathogenic (Apr 10, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000887886

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Jun 29, 2018)

unknown

clinical testing

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

SCV001779196

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 28, 2023)

germline

clinical testing

Citation Link,

SCV004565026

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Pathogenic
(Apr 10, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Comprehensive mutational analysis of BRCA1/BRCA2 for Korean breast cancer patients: evidence of a founder mutation.

Seong MW, Cho S, Noh DY, Han W, Kim SW, Park CM, Park HW, Kim SY, Kim JY, Park SS.

Clin Genet. 2009 Aug;76(2):152-60. doi: 10.1111/j.1399-0004.2009.01202.x. Epub 2009 Jul 28.

PubMed [citation]

PMID:: 19656164

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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000887886.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. Additionally, this variant has been reported in an individual with breast cancer in the published literature (PMID: 19656164 (2009)). Based on the available information, this variant is classified as pathogenic.

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

From GeneDx, SCV001779196.2

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Reported in association with hereditary breast and ovarian cancer, and identified as a recurrent pathogenic variant in individuals of Korean ancestry (Han et al., 2011; Kwong et al., 2016; Ryu et al., 2019); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at a significant frequency in large population cohorts (gnomAD); Also known as 6952_6953del; This variant is associated with the following publications: (PMID: 25863477, 29922827, 19656164, 27836010, 26187060, 29446198, 22798144, 29346284, 30350268, 21497495, 30720243, 31447099, 34645131)

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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV004565026.1

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

Description

The BRCA2 c.6724_6725del; p.Asp2242PhefsTer2 variant (rs397507375), also known as 6952delGA, is reported in individuals with breast cancer (Bang 2022, Ryu 2019, Seong 2009). This variant is also reported in ClinVar (Variation ID: 38062). It is only found on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting two nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Bang YJ et al. Clinicopathological Characterization of Double Heterozygosity for BRCA1 and BRCA2 Variants in Korean Breast Cancer Patients. Cancer Res Treat. 2022 Jul;54(3):827-833. PMID: 34645131. Ryu JM et al. Prevalence and oncologic outcomes of BRCA 1/2 mutations in unselected triple-negative breast cancer patients in Korea. Breast Cancer Res Treat. 2019 Jan;173(2):385-395. PMID: 30350268. Seong MW et al. Comprehensive mutational analysis of BRCA1/BRCA2 for Korean breast cancer patients: evidence of a founder mutation. Clin Genet. 2009 Aug;76(2):152-60. PMID: 19656164.

#	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: May 3, 2025

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