NM_005431.2(XRCC2):c.808T>G (p.Phe270Val) AND not specified

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Jun 23, 2021
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:: RCV000115899.12

Allele description [Variation Report for NM_005431.2(XRCC2):c.808T>G (p.Phe270Val)]

NM_005431.2(XRCC2):c.808T>G (p.Phe270Val)

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.808T>G (p.Phe270Val)

Other names:

p.F270V:TTT>GTT

HGVS:

NC_000007.14:g.152648677A>C
NG_027988.2:g.32489T>G
NM_005431.2:c.808T>GMANE SELECT
NP_005422.1:p.Phe270Val
LRG_323t1:c.808T>G
LRG_323:g.32489T>G
LRG_323p1:p.Phe270Val
NC_000007.13:g.152345762A>C
NG_027988.1:g.32489T>G
NM_005431.1:c.808T>G
O43543:p.Phe270Val

Protein change:

F270V

Links:

UniProtKB: O43543#VAR_077186; dbSNP: rs145085742

NCBI 1000 Genomes Browser:

rs145085742

Molecular consequence:

NM_005431.2:c.808T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000149808	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely benign (Dec 19, 2017)	germline	clinical testing	Citation Link,
SCV002066409	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jun 23, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000149808

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely benign
(Dec 19, 2017)

germline

clinical testing

Citation Link,

SCV002066409

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jun 23, 2021)

germline

clinical testing

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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 GeneDx, SCV000149808.8

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#	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 Genetic Services Laboratory, University of Chicago, SCV002066409.1

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

Description

DNA sequence analysis of the XRCC2 gene demonstrated a sequence change, c.808T>G, in exon 3 that results in an amino acid change, p.Phe270Val. This sequence change does not appear to have been previously described in patients with XRCC2-related disorders and has been described in the gnomAD database with a low population frequency of 0.70% in African subpopulation (dbSNP rs145085742). The p.Phe270Val change affects a highly conserved amino acid residue located in a domain of the XRCC2 protein that is not known to be functional. The p.Phe270Val substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Phe270Val change remains unknown at this time.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

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