NM_000059.4(BRCA2):c.8639_8640del (p.Thr2880fs) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 8, 2016
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000241244.14

Allele description [Variation Report for NM_000059.4(BRCA2):c.8639_8640del (p.Thr2880fs)]

NM_000059.4(BRCA2):c.8639_8640del (p.Thr2880fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.8639_8640del (p.Thr2880fs)

HGVS:

NC_000013.10:g.32950813_32950814del
NC_000013.11:g.32376674CA[1]
NG_012772.3:g.66195CA[1]
NM_000059.4:c.8639_8640delMANE SELECT
NP_000050.3:p.Thr2880fs
LRG_293:g.66195CA[1]
NC_000013.10:g.32950810_32950811del
NC_000013.10:g.32950811CA[1]
NC_000013.10:g.32950813_32950814del
NM_000059.3:c.8639_8640delCA
NM_000059.4:c.8639_8640del

Protein change:

T2880fs

Links:

dbSNP: rs886038184

NCBI 1000 Genomes Browser:

rs886038184

Molecular consequence:

NM_000059.4:c.8639_8640del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Breast-ovarian cancer, familial, susceptibility to, 2 (BROVCA2)
Synonyms:: Breast-ovarian cancer, familial 2
Identifiers:: MONDO: MONDO:0012933; MedGen: C2675520; Orphanet: 145; OMIM: 612555

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S-phase kinase-associated protein 1 [Drosophila sechellia]
S-phase kinase-associated protein 1 [Drosophila sechellia]
gi|1818137375|ref|XP_032575337.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000301299	Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	reviewed by expert panel (ENIGMA BRCA1/2 Classification Criteria (2015))	Pathogenic (Sep 8, 2016)	germline	curation	ENIGMA BRCA1/2 Classification Criteria (2015), Citation Link,
SCV000327941	Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	criteria provided, single submitter (CIMBA Mutation Classification guidelines May 2016)	Pathogenic (Oct 2, 2015)	germline	clinical testing	CIMBA_Mutation_Classification_guidelines_May16.pdf, Citation Link,
SCV004846048	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 15, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25863477, 29446198, 32341426, 32939053, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000301299

Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)

reviewed by expert panel

(ENIGMA BRCA1/2 Classification Criteria (2015))

Pathogenic
(Sep 8, 2016)

germline

curation

ENIGMA BRCA1/2 Classification Criteria (2015),

Citation Link,

SCV000327941

Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge

criteria provided, single submitter

(CIMBA Mutation Classification guidelines May 2016)

Pathogenic
(Oct 2, 2015)

germline

clinical testing

CIMBA_Mutation_Classification_guidelines_May16.pdf,

Citation Link,

SCV004846048

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 15, 2023)

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	1	1	not provided	108544	not provided	clinical testing, curation

Citations

PubMed

The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean Hereditary Breast Cancer (KOHBRA) study.

Kang E, Seong MW, Park SK, Lee JW, Lee J, Kim LS, Lee JE, Kim SY, Jeong J, Han SA, Kim SW; Korean Hereditary Breast Cancer Study Group..

Breast Cancer Res Treat. 2015 May;151(1):157-68. doi: 10.1007/s10549-015-3377-4. Epub 2015 Apr 12.

PubMed [citation]

PMID:: 25863477

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

Rebbeck TR, Friebel TM, Friedman E, Hamann U, Huo D, Kwong A, Olah E, Olopade OI, Solano AR, Teo SH, Thomassen M, Weitzel JN, Chan TL, Couch FJ, Goldgar DE, Kruse TA, Palmero EI, Park SK, Torres D, van Rensburg EJ, McGuffog L, Parsons MT, et al.

Hum Mutat. 2018 May;39(5):593-620. doi: 10.1002/humu.23406. Epub 2018 Mar 12.

PubMed [citation]

PMID:: 29446198
PMCID:: PMC5903938

See all PubMed Citations (5)

Details of each submission

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000301299.2

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

Description

Variant allele predicted to encode a truncated non-functional protein.

#	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 Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge, SCV000327941.4

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

#	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	1	not provided

From All of Us Research Program, National Institutes of Health, SCV004846048.1

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

Description

This variant is predicted to result in loss of protein function through nonsense-mediated or protein truncation. Loss of function is an established mechanism of disease. This prediction has not been confirmed by functional studies. This variant has been reported in multiple individuals with Hereditary breast and ovarian cancer (PMID: 25863477, 32939053, 32341426, 29446198). This variant is absent from or rare in large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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