NM_000059.4(BRCA2):c.8677C>T (p.Gln2893Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 4, 2020
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:: RCV000413575.12

Allele description [Variation Report for NM_000059.4(BRCA2):c.8677C>T (p.Gln2893Ter)]

NM_000059.4(BRCA2):c.8677C>T (p.Gln2893Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.8677C>T (p.Gln2893Ter)

HGVS:

NC_000013.11:g.32376714C>T
NG_012772.3:g.66235C>T
NM_000059.4:c.8677C>TMANE SELECT
NP_000050.2:p.Gln2893Ter
NP_000050.3:p.Gln2893Ter
LRG_293t1:c.8677C>T
LRG_293:g.66235C>T
LRG_293p1:p.Gln2893Ter
NC_000013.10:g.32950851C>T
NM_000059.3:c.8677C>T

Nucleotide change:

8905C>T

Protein change:

Q2893*

Links:

dbSNP: rs397507409

NCBI 1000 Genomes Browser:

rs397507409

Molecular consequence:

NM_000059.4:c.8677C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000490437	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Dec 6, 2018)	germline	clinical testing	Citation Link,
SCV002046160	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Oct 4, 2020)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9609997, 29446198, 26187060, 24249303, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000490437

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Dec 6, 2018)

germline

clinical testing

Citation Link,

SCV002046160

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Oct 4, 2020)

unknown

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	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

Citations

PubMed

High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families.

Katagiri T, Kasumi F, Yoshimoto M, Nomizu T, Asaishi K, Abe R, Tsuchiya A, Sugano M, Takai S, Yoneda M, Fukutomi T, Nanba K, Makita M, Okazaki H, Hirata K, Okazaki M, Furutsuma Y, Morishita Y, Iino Y, Karino T, Ayabe H, Hara S, et al.

J Hum Genet. 1998;43(1):42-8.

PubMed [citation]

PMID:: 9609997

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 GeneDx, SCV000490437.3

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

Description

This variant is denoted BRCA2 c.8677C>T at the cDNA level and p.Gln2893Ter (Q2893X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also known as BRCA2 8905C>T using alternate nomenclature, has been reported in association with Hereditary Breast and Ovarian Cancer syndrome (Katagiri 1998, Laitman 2011, Takahashi 2017) and is considered pathogenic.

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002046160.2

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

Description

This nonsense variant causes the premature termination of BRCA2 protein synthesis. In addition, it has been reported in individuals and families affected breast or ovarian cancer in the published literature (PMID: 29446198 (2018), 24249303 (2015), 9609997 (1998)). Therefore, the variant is classified as pathogenic and this individual is at increased risk of developing BRCA2 related cancers.

#	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

Last Updated: Nov 24, 2024

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