NM_000059.4(BRCA2):c.8905G>A (p.Val2969Met) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Benign (7 submissions)
Last evaluated:: Aug 10, 2015
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:: RCV000077456.23

Allele description [Variation Report for NM_000059.4(BRCA2):c.8905G>A (p.Val2969Met)]

NM_000059.4(BRCA2):c.8905G>A (p.Val2969Met)

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.8905G>A (p.Val2969Met)

Other names:

p.V2969M:GTG>ATG; 9133G>A

HGVS:

NC_000013.11:g.32379467G>A
NG_012772.3:g.68988G>A
NM_000059.4:c.8905G>AMANE SELECT
NP_000050.2:p.Val2969Met
NP_000050.3:p.Val2969Met
LRG_293t1:c.8905G>A
LRG_293:g.68988G>A
LRG_293p1:p.Val2969Met
NC_000013.10:g.32953604G>A
NM_000059.3:c.8905G>A
U43746.1:n.9133G>A
p.V2969M

Protein change:

V2969M

Links:

dbSNP: rs59004709

NCBI 1000 Genomes Browser:

rs59004709

Molecular consequence:

NM_000059.4:c.8905G>A - missense variant - [Sequence Ontology: SO:0001583]

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

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zinc finger protein 354C [Homo sapiens]
zinc finger protein 354C [Homo sapiens]
gi|30794504|ref|NP_055409.1|

Protein
Mus musculus solute carrier family 6 (neurotransmitter transporter, glycine), me...
Mus musculus solute carrier family 6 (neurotransmitter transporter, glycine), member 9 (Slc6a9), transcript variant 1, mRNA
gi|116686111|ref|NM_008135.4|

Nucleotide
sodium- and chloride-dependent glycine transporter 1 isoform 1 [Mus musculus]
sodium- and chloride-dependent glycine transporter 1 isoform 1 [Mus musculus]
gi|71067352|ref|NP_032161.2|

Protein
Homo sapiens long intergenic non-protein coding RNA 1806 (LINC01806), transcript...
Homo sapiens long intergenic non-protein coding RNA 1806 (LINC01806), transcript variant 1, long non-coding RNA
gi|571330806|ref|NR_110163.1|

Nucleotide
RecName: Full=Ubiquinol-cytochrome c reductase complex assembly factor 6; AltNam...
RecName: Full=Ubiquinol-cytochrome c reductase complex assembly factor 6; AltName: Full=Protein BRAWNIN
gi|284018073|sp|Q69YU5.2|UQCC6_HUMA

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000109254	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Uncertain significance (Nov 6, 2006)	germline	clinical testing
SCV000147483	Breast Cancer Information Core (BIC) (BRCA2)	no assertion criteria provided	Uncertain significance (May 29, 2002)	germline	clinical testing
SCV000154091	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Likely benign (Mar 20, 2014)	unknown	literature only	PubMed (3) [See all records that cite these PMIDs] 17924331, 9971877, 19043619 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV000244488	Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	reviewed by expert panel (ENIGMA BRCA1/2 Classification Criteria (2015))	Benign (Aug 10, 2015)	germline	curation	PubMed (1) [See all records that cite this PMID] ENIGMA BRCA1/2 Classification Criteria (2015), Citation Link,
SCV001270520	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV004243838	BRCAlab, Lund University	no assertion criteria provided	Benign (Mar 2, 2020)	germline	clinical testing
SCV004846091	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Benign (Jan 11, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	8	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	54	not provided	not provided	108544	not provided	clinical testing, curation
not provided	germline	not provided	1	not provided	not provided	1	not provided	clinical testing
	unknown	unknown	not provided	not provided	not provided	not provided	not provided	literature only
Asian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Canadian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Central/Eastern European	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
Mixed European	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Western European	germline	yes	8	not provided	not provided	not provided	not provided	clinical testing
Western European, German	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Western Europeanan, Central/Eastern European	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes.

Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K, Tavtigian SV, Monteiro AN, Iversen ES, Couch FJ, Goldgar DE.

Am J Hum Genet. 2007 Nov;81(5):873-83. Epub 2007 Sep 6.

PubMed [citation]

PMID:: 17924331
PMCID:: PMC2265654

Global sequence diversity of BRCA2: analysis of 71 breast cancer families and 95 control individuals of worldwide populations.

Wagner TM, Hirtenlehner K, Shen P, Moeslinger R, Muhr D, Fleischmann E, Concin H, Doeller W, Haid A, Lang AH, Mayer P, Petru E, Ropp E, Langbauer G, Kubista E, Scheiner O, Underhill P, Mountain J, Stierer M, Zielinski C, Oefner P.

Hum Mol Genet. 1999 Mar;8(3):413-23. Erratum in: Hum Mol Genet 1999 Apr;8(4):717-9.

PubMed [citation]

PMID:: 9971877

See all PubMed Citations (5)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000109254.3

#	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), SCV000147483.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	7	not provided	not provided	clinical testing	not provided
2	not provided	1	not provided	not provided	clinical testing	not provided
3	Asian	1	not provided	not provided	clinical testing	not provided
4	Canadian	1	not provided	not provided	clinical testing	not provided
5	Central/Eastern European	3	not provided	not provided	clinical testing	not provided
6	Mixed European	1	not provided	not provided	clinical testing	not provided
7	Western European	8	not provided	not provided	clinical testing	not provided
8	Western European, German	1	not provided	not provided	clinical testing	not provided
9	Western Europeanan, Central/Eastern 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		7	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		1	not provided	not provided	not provided
4	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
5	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided
6	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
7	germline	yes	not provided	not provided	not provided		8	not provided	not provided	not provided
8	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
9	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Counsyl, SCV000154091.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		not provided	not provided	not provided	literature only	PubMed (3)

#	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

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000244488.1

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

Description

IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000011

#	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 Illumina Laboratory Services, Illumina, SCV001270520.1

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#	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 BRCAlab, Lund University, SCV004243838.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From All of Us Research Program, National Institutes of Health, SCV004846091.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	54	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		54	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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