NM_000059.4(BRCA2):c.7888A>C (p.Lys2630Gln) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 23, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001290194.1

Allele description [Variation Report for NM_000059.4(BRCA2):c.7888A>C (p.Lys2630Gln)]

NM_000059.4(BRCA2):c.7888A>C (p.Lys2630Gln)

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.7888A>C (p.Lys2630Gln)

HGVS:

NC_000013.11:g.32362605A>C
NG_012772.3:g.52126A>C
NM_000059.4:c.7888A>CMANE SELECT
NP_000050.3:p.Lys2630Gln
LRG_293t1:c.7888A>C
LRG_293:g.52126A>C
NC_000013.10:g.32936742A>C
NM_000059.3:c.7888A>C

Protein change:

K2630Q

Links:

dbSNP: rs1380792392

NCBI 1000 Genomes Browser:

rs1380792392

Molecular consequence:

NM_000059.4:c.7888A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001478292	Cancer Variant Interpretation Group UK, Institute of Cancer Research, London	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 23, 2018)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 29394989, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001478292

Cancer Variant Interpretation Group UK, Institute of Cancer Research, London

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 23, 2018)

germline

curation

PubMed (2)
[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	curation

Citations

PubMed

Assessment of the Clinical Relevance of BRCA2 Missense Variants by Functional and Computational Approaches.

Guidugli L, Shimelis H, Masica DL, Pankratz VS, Lipton GB, Singh N, Hu C, Monteiro ANA, Lindor NM, Goldgar DE, Karchin R, Iversen ES, Couch FJ.

Am J Hum Genet. 2018 Feb 1;102(2):233-248. doi: 10.1016/j.ajhg.2017.12.013. Epub 2018 Jan 25.

PubMed [citation]

PMID:: 29394989
PMCID:: PMC5985401

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Cancer Variant Interpretation Group UK, Institute of Cancer Research, London, SCV001478292.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)

Description

Data used in classification: The frequency of this variant is 0/138,632 individuals (tgnomAD) (PM2_mod). This variant is predicted deleterious on AlignGVGD (class: C45), SIFT (Deleterious), Polyphen2 HumVar (probably damaging) and CADD (27.5) (PP3_sup). The variant is in the DNA-binding domain of BRCA2 (PM1_sup). In the VarCall Bayesian statistical model for VUS classification using functional assay data (Guidugli et al Am J Hum Genet 2018; 102:233-248, Couch Lab), the variant has a probability of being deleterious of 0.972 and an overall classification of pathogenic. (PS3_strong). Data not used in classification: There are no reports of this variant in ClinVar, BIC or BRCA2 LOVD.

#	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: Sep 1, 2024

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