NM_000059.4(BRCA2):c.2224C>T (p.Gln742Ter) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Pathogenic (6 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:: RCV000077273.18

Allele description [Variation Report for NM_000059.4(BRCA2):c.2224C>T (p.Gln742Ter)]

NM_000059.4(BRCA2):c.2224C>T (p.Gln742Ter)

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.2224C>T (p.Gln742Ter)

Other names:

p.Q742*:CAA>TAA

HGVS:

NC_000013.11:g.32336579C>T
NG_012772.3:g.26100C>T
NM_000059.4:c.2224C>TMANE SELECT
NP_000050.2:p.Gln742Ter
NP_000050.3:p.Gln742Ter
LRG_293t1:c.2224C>T
LRG_293:g.26100C>T
LRG_293p1:p.Gln742Ter
NC_000013.10:g.32910716C>T
NM_000059.3:c.2224C>T
U43746.1:n.2452C>T
p.Gln742*

Nucleotide change:

2452C>T

Protein change:

Q742*

Links:

dbSNP: rs80358494

NCBI 1000 Genomes Browser:

rs80358494

Molecular consequence:

NM_000059.4:c.2224C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000109070	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Pathogenic (Feb 26, 2013)	germline	clinical testing
SCV000146017	Breast Cancer Information Core (BIC) (BRCA2)	no assertion criteria provided	Pathogenic (May 29, 2002)	germline	clinical testing
SCV000300498	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,
SCV000326673	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,
SCV001190320	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - AGHI GT	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 25, 2019)	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV004847023	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 19, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 16030099, 18284688, 25628955, 25716084, 26543556, 26681312, 29446198, 35875314, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	3	3	not provided	108544	not provided	clinical testing, curation
not provided	germline	not provided	6	not provided	not provided	6	not provided	clinical testing
not provided	unknown	unknown	1	not provided	not provided	1	not provided	research
Latin American, Caribbean	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Latin American, Caribbean, Western European	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Prevalence of BRCA mutations and founder effect in high-risk Hispanic families.

Weitzel JN, Lagos V, Blazer KR, Nelson R, Ricker C, Herzog J, McGuire C, Neuhausen S.

Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1666-71.

PubMed [citation]

PMID:: 16030099

Evaluation of unclassified variants in the breast cancer susceptibility genes BRCA1 and BRCA2 using five methods: results from a population-based study of young breast cancer patients.

Lee E, McKean-Cowdin R, Ma H, Chen Z, Van Den Berg D, Henderson BE, Bernstein L, Ursin G.

Breast Cancer Res. 2008;10(1):R19. doi: 10.1186/bcr1865. Epub 2008 Feb 19.

PubMed [citation]

PMID:: 18284688
PMCID:: PMC2374975

See all PubMed Citations (9)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000109070.3

#	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	not provided	6	not provided	not provided		not provided	not provided	not provided	not provided

From Breast Cancer Information Core (BIC) (BRCA2), SCV000146017.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Latin American, Caribbean	1	not provided	not provided	clinical testing	not provided
2	Latin American, Caribbean, Western European	1	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	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
2	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000300498.2

#	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, SCV000326673.4

#	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	3	not provided

From HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - AGHI GT, SCV001190320.1

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

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

From All of Us Research Program, National Institutes of Health, SCV004847023.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (9)

Description

This variant changes 1 nucleotide in exon 11 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 at least five individuals affected with breast cancer (PMID: 18284688, 25628955, 25716084, 26543556, 26681312, 35875314) and in four suspected hereditary breast and ovarian cancer families (PMID: 16030099, 29446198). This variant has been identified in 1/251260 chromosomes 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	108544	not provided	not provided		3	not provided	not provided	not provided

Last Updated: Oct 26, 2024

ClinVar

Relating variation to medicine