NM_000059.4(BRCA2):c.2835dup (p.Asp946fs) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 22, 2022
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:: RCV002515624.9

Allele description [Variation Report for NM_000059.4(BRCA2):c.2835dup (p.Asp946fs)]

NM_000059.4(BRCA2):c.2835dup (p.Asp946fs)

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.2835dup (p.Asp946fs)

HGVS:

NC_000013.11:g.32337190dup
NG_012772.3:g.26711dup
NM_000059.4:c.2835dupMANE SELECT
NM_000059.4:c.2835dupA
NP_000050.3:p.Asp946fs
LRG_293:g.26711dup
NC_000013.10:g.32911321_32911322insA
NC_000013.10:g.32911327dup
NM_000059.3:c.2835dupA
p.(Asp946ArgfsTer13)

Protein change:

D946fs

Links:

dbSNP: rs80359356

NCBI 1000 Genomes Browser:

rs80359356

Molecular consequence:

NM_000059.4:c.2835dup - 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
SCV003442033	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 22, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 28724667, 30702160, 31825140, 20104584, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003442033

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 22, 2022)

germline

clinical testing

PubMed (5)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients.

Sun J, Meng H, Yao L, Lv M, Bai J, Zhang J, Wang L, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B, Xie Y.

Clin Cancer Res. 2017 Oct 15;23(20):6113-6119. doi: 10.1158/1078-0432.CCR-16-3227. Epub 2017 Jul 19.

PubMed [citation]

PMID:: 28724667

Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients.

Bhaskaran SP, Chandratre K, Gupta H, Zhang L, Wang X, Cui J, Kim YC, Sinha S, Jiang L, Lu B, Wu X, Qin Z, Huang T, Wang SM.

Int J Cancer. 2019 Aug 15;145(4):962-973. doi: 10.1002/ijc.32176. Epub 2019 Feb 13.

PubMed [citation]

PMID:: 30702160
PMCID:: PMC6617753

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV003442033.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 231432). This variant is also known as 2830dupA, c.2829_2830insA. This premature translational stop signal has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 28724667, 30702160, 31825140). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp946Argfs*13) 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).

#	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: Jun 29, 2024

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