NM_000059.4(BRCA2):c.4222C>T (p.Gln1408Ter) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Pathogenic (5 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:: RCV000031470.18

Allele description [Variation Report for NM_000059.4(BRCA2):c.4222C>T (p.Gln1408Ter)]

NM_000059.4(BRCA2):c.4222C>T (p.Gln1408Ter)

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.4222C>T (p.Gln1408Ter)

HGVS:

NC_000013.11:g.32338577C>T
NG_012772.3:g.28098C>T
NM_000059.4:c.4222C>TMANE SELECT
NP_000050.2:p.Gln1408Ter
NP_000050.3:p.Gln1408Ter
LRG_293t1:c.4222C>T
LRG_293:g.28098C>T
LRG_293p1:p.Gln1408Ter
NC_000013.10:g.32912714C>T
NM_000059.3:c.4222C>T
U43746.1:n.4450C>T
p.Gln1408*

Nucleotide change:

4450C>T

Protein change:

Q1408*

Links:

dbSNP: rs80358663

NCBI 1000 Genomes Browser:

rs80358663

Molecular consequence:

NM_000059.4:c.4222C>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000054075	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Pathogenic (Mar 16, 2010)	germline	clinical testing
SCV000146393	Breast Cancer Information Core (BIC) (BRCA2)	no assertion criteria provided	Pathogenic (Dec 23, 2003)	germline	clinical testing
SCV000300724	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,
SCV000326991	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,
SCV004845284	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 31, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19818148, 22009639, 29446198, 34072659, 25741868

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	1	14	not provided	108544	not provided	clinical testing, curation
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Caucasian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Western European	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Selecting for BRCA1 testing using a combination of homogeneous selection criteria and immunohistochemical characteristics of breast cancers.

Miolo G, Canzonieri V, De Giacomi C, Puppa LD, Dolcetti R, Lombardi D, Perin T, Scalone S, Veronesi A, Viel A.

BMC Cancer. 2009 Oct 10;9:360. doi: 10.1186/1471-2407-9-360.

PubMed [citation]

PMID:: 19818148
PMCID:: PMC2771044

Predictive factors for BRCA1/BRCA2 mutations in women with ductal carcinoma in situ.

Bayraktar S, Elsayegh N, Gutierrez Barrera AM, Lin H, Kuerer H, Tasbas T, Muse KI, Ready K, Litton J, Meric-Bernstam F, Hortobagyi GN, Albarracin CT, Arun B.

Cancer. 2012 Mar 15;118(6):1515-22. doi: 10.1002/cncr.26428. Epub 2011 Aug 25. Erratum in: Cancer. 2014 Mar 15;120(6):927.

PubMed [citation]

PMID:: 22009639
PMCID:: PMC4407692

See all PubMed Citations (5)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000054075.3

#	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	1	not provided	not provided		not provided	not provided	not provided	not provided

From Breast Cancer Information Core (BIC) (BRCA2), SCV000146393.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided
2	Caucasian	1	not provided	not provided	clinical testing	not provided
3	Western European	2	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
3	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000300724.2

#	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, SCV000326991.4

#	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	14	not provided

From All of Us Research Program, National Institutes of Health, SCV004845284.1

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

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 1 individual affected with ovarian cancer and 2 individuals affected with breast cancer (PMID: 19818148, 22009639, 34072659). This variant has been identified in 27 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	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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