NM_000059.4(BRCA2):c.8677C>T (p.Gln2893Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 21, 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:: RCV001018169.12

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)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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LOC115463315 [Microcaecilia unicolor]
LOC115463315 [Microcaecilia unicolor]
Gene ID:115463315

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001179365	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (May 26, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20960228, 24249303, 26187060, 29446198, 9609997 Citation Link,
SCV004362769	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 21, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 9609997, 19806429, 24249303, 27271530, 29446198, 31469826, 32816949, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001179365

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(May 26, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link,

SCV004362769

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 21, 2023)

germline

clinical testing

PubMed (8)
[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 BRCA1 and BRCA2 genes in ethnically diverse high risk families in Israel.

Laitman Y, Borsthein RT, Stoppa-Lyonnet D, Dagan E, Castera L, Goislard M, Gershoni-Baruch R, Goldberg H, Kaufman B, Ben-Baruch N, Zidan J, Maray T, Soussan-Gutman L, Friedman E.

Breast Cancer Res Treat. 2011 Jun;127(2):489-95. doi: 10.1007/s10549-010-1217-0. Epub 2010 Oct 20.

PubMed [citation]

PMID:: 20960228

Comprehensive spectrum of BRCA1 and BRCA2 deleterious mutations in breast cancer in Asian countries.

Kwong A, Shin VY, Ho JC, Kang E, Nakamura S, Teo SH, Lee AS, Sng JH, Ginsburg OM, Kurian AW, Weitzel JN, Siu MT, Law FB, Chan TL, Narod SA, Ford JM, Ma ES, Kim SW.

J Med Genet. 2016 Jan;53(1):15-23. doi: 10.1136/jmedgenet-2015-103132. Epub 2015 Jul 17. Review.

PubMed [citation]

PMID:: 26187060
PMCID:: PMC4681590

See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV001179365.4

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

Description

The p.Q2893* variant (also known as c.8677C>T), located in coding exon 20 of the BRCA2 gene, results from a C to T substitution at nucleotide position 8677. This changes the amino acid from a glutamine to a stop codon within coding exon 20. This mutation (designated as "Gln 2893 ter") was reported in a family from Japan with hereditary breast cancer (Katagiri T et al. J. Hum. Genet. 1998;43:42-8). This alteration was also identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat. 2018 05;39:593-620). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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 Color Diagnostics, LLC DBA Color Health, SCV004362769.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This variant changes 1 nucleotide in exon 21 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in 1 individual affected with pancreatic cancer and 1 individual affected with breast cancer (PMID: 27271530, 31469826, 32816949). This variant has been reported in at least 1 family with multiple individuals affected with breast cancer (PMID: 24249303, 19806429, 9609997) and has been identified in 3 families among the CIMBA participants (PMID: 29446198). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#	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: Oct 13, 2024

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