NM_005431.2(XRCC2):c.659A>T (p.Asp220Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 30, 2023
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:: RCV001066340.10

Allele description [Variation Report for NM_005431.2(XRCC2):c.659A>T (p.Asp220Val)]

NM_005431.2(XRCC2):c.659A>T (p.Asp220Val)

Gene:

XRCC2:X-ray repair cross complementing 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q36.1

Genomic location:

Preferred name:

NM_005431.2(XRCC2):c.659A>T (p.Asp220Val)

HGVS:

NC_000007.14:g.152648826T>A
NG_027988.2:g.32340A>T
NM_005431.2:c.659A>TMANE SELECT
NP_005422.1:p.Asp220Val
LRG_323t1:c.659A>T
LRG_323:g.32340A>T
LRG_323p1:p.Asp220Val
NC_000007.13:g.152345911T>A
NG_027988.1:g.32340A>T
NM_005431.1:c.659A>T

Protein change:

D220V

Links:

dbSNP: rs765021741

NCBI 1000 Genomes Browser:

rs765021741

Molecular consequence:

NM_005431.2:c.659A>T - 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
SCV001231347	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 30, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23054243, 27233470, 28492532
SCV001364738	Leiden Open Variation Database	no assertion criteria provided	Uncertain significance (Apr 14, 2016)	germline	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001231347

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 30, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001364738

Leiden Open Variation Database

no assertion criteria provided

Uncertain significance
(Apr 14, 2016)

germline

curation

PubMed (1)
[See all records that cite this PMID]

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	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Functional Analysis of Missense Variants in the Putative Breast Cancer Susceptibility Gene XRCC2.

Hilbers FS, Luijsterburg MS, Wiegant WW, Meijers CM, Völker-Albert M, Boonen RA, van Asperen CJ, Devilee P, van Attikum H.

Hum Mutat. 2016 Sep;37(9):914-25. doi: 10.1002/humu.23019. Epub 2016 Jun 17.

PubMed [citation]

PMID:: 27233470

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001231347.5

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

Description

An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 220 of the XRCC2 protein (p.Asp220Val). This variant is present in population databases (rs765021741, gnomAD 0.0009%). This missense change has been observed in individual(s) with breast cancer (PMID: 23054243). ClinVar contains an entry for this variant (Variation ID: 486728). Experimental studies have shown that this missense change does not substantially affect XRCC2 function (PMID: 27233470). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Leiden Open Variation Database, SCV001364738.1

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

Description

Curator: Arleen D. Auerbach. Submitter to LOVD: Florentine Hilbers.

#	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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