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NM_005431.2(XRCC2):c.659A>T (p.Asp220Val) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 24, 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:
RCV000567327.4

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)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000675848Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Uncertain significance
(Mar 24, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Rare variants in XRCC2 as breast cancer susceptibility alleles.

Hilbers FS, Wijnen JT, Hoogerbrugge N, Oosterwijk JC, Collee MJ, Peterlongo P, Radice P, Manoukian S, Feroce I, Capra F, Couch FJ, Wang X, Guidugli L, Offit K, Shah S, Campbell IG, Thompson ER, James PA, Trainer AH, Gracia J, Benitez J, van Asperen CJ, et al.

J Med Genet. 2012 Oct;49(10):618-20. doi: 10.1136/jmedgenet-2012-101191.

PubMed [citation]
PMID:
23054243

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

Details of each submission

From Ambry Genetics, SCV000675848.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The p.D220V variant (also known as c.659A>T), located in coding exon 3 of the XRCC2 gene, results from an A to T substitution at nucleotide position 659. The aspartic acid at codon 220 is replaced by valine, an amino acid with highly dissimilar properties. This alteration was identified in 1/3548 BRCA1/2-negative familial breast cancer cases and 0/1435 controls (Hilbers FS et al. J. Med. Genet., 2012 Oct;49:618-20). A cDNA complementation assay showed that the DNA repair efficiency of this alteration is similar to wild type (Hilbers FS et al. Hum. Mutat., 2016 09;37:914-25). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 28, 2024