NM_000059.4(BRCA2):c.7464A>C (p.Arg2488Ser) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 9, 2019
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:: RCV000759655.5

Allele description [Variation Report for NM_000059.4(BRCA2):c.7464A>C (p.Arg2488Ser)]

NM_000059.4(BRCA2):c.7464A>C (p.Arg2488Ser)

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.7464A>C (p.Arg2488Ser)

HGVS:

NC_000013.11:g.32356456A>C
NG_012772.3:g.45977A>C
NM_000059.4:c.7464A>CMANE SELECT
NP_000050.2:p.Arg2488Ser
NP_000050.3:p.Arg2488Ser
LRG_293t1:c.7464A>C
LRG_293:g.45977A>C
LRG_293p1:p.Arg2488Ser
NC_000013.10:g.32930593A>C
NM_000059.3:c.7464A>C
U43746.1:n.7692A>C
p.R2488S

Nucleotide change:

7692A>C

Protein change:

R2488S

Links:

dbSNP: rs80358969

NCBI 1000 Genomes Browser:

rs80358969

Molecular consequence:

NM_000059.4:c.7464A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000889126	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Feb 20, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 29394989, 19043619, 29884841, 26467025
SCV001776388	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Oct 9, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000889126

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Feb 20, 2019)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001776388

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Oct 9, 2019)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

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

Classifying Variants of Undetermined Significance in BRCA2 with protein likelihood ratios.

Karchin R, Agarwal M, Sali A, Couch F, Beattie MS.

Cancer Inform. 2008;6:203-16. Epub 2008 Apr 18.

PubMed [citation]

PMID:: 19043619
PMCID:: PMC2587343

See all PubMed Citations (4)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000889126.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

#	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 GeneDx, SCV001776388.1

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

Description

Published functional studies demonstrate no damaging effect: homology-directed repair activity consistent with neutrality (Guidugli 2018); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not observed at a significant frequency in large population cohorts (Lek 2016); Also known as: BRCA2 7692A>C; This variant is associated with the following publications: (PMID: 29884841, 31422574, 19043619, 29394989)

#	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

Last Updated: Sep 29, 2024

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