NM_000059.4(BRCA2):c.6682dup (p.Val2228fs) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 30, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000496313.14

Allele description [Variation Report for NM_000059.4(BRCA2):c.6682dup (p.Val2228fs)]

NM_000059.4(BRCA2):c.6682dup (p.Val2228fs)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.6682dup (p.Val2228fs)

Other names:

6910insG

HGVS:

NC_000013.11:g.32341037dup
NG_012772.3:g.30558dup
NM_000059.4:c.6682dupMANE SELECT
NM_000059.4:c.6682dupG
NP_000050.3:p.Val2228fs
LRG_293t1:c.6682dup
LRG_293:g.30558dup
NC_000013.10:g.32915173_32915174insG
NC_000013.10:g.32915174dup
NM_000059.3:c.6682dup
NM_000059.3:c.6682dupG
U43746.1:n.6910_6911insG

Protein change:

V2228fs

Links:

Breast Cancer Information Core (BIC) (BRCA2): 6910&base_change=ins G; dbSNP: rs80359621

NCBI 1000 Genomes Browser:

rs80359621

Molecular consequence:

NM_000059.4:c.6682dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000587864	Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR)	no assertion criteria provided	Pathogenic (Jan 31, 2014)	germline	research
SCV001582296	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 30, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15131399, 25682074, 20104584, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000587864

Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR)

no assertion criteria provided

Pathogenic
(Jan 31, 2014)

germline

research

SCV001582296

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 30, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer.

Wong-Brown MW, Meldrum CJ, Carpenter JE, Clarke CL, Narod SA, Jakubowska A, Rudnicka H, Lubinski J, Scott RJ.

Breast Cancer Res Treat. 2015 Feb;150(1):71-80. doi: 10.1007/s10549-015-3293-7. Epub 2015 Feb 15.

PubMed [citation]

PMID:: 25682074

See all PubMed Citations (4)

Details of each submission

From Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR), SCV000587864.1

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

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001582296.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 15131399, 25682074). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val2228Glyfs*5) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 52155). This variant is also known as c.6909insG.

#	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 24, 2024

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