NM_005431.2(XRCC2):c.773G>A (p.Arg258His) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Jan 9, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000567423.6

Allele description [Variation Report for NM_005431.2(XRCC2):c.773G>A (p.Arg258His)]

NM_005431.2(XRCC2):c.773G>A (p.Arg258His)

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.773G>A (p.Arg258His)

Other names:

p.R258H:CGT>CAT

HGVS:

NC_000007.14:g.152648712C>T
NG_027988.2:g.32454G>A
NM_005431.2:c.773G>AMANE SELECT
NP_005422.1:p.Arg258His
LRG_323t1:c.773G>A
LRG_323:g.32454G>A
LRG_323p1:p.Arg258His
NC_000007.13:g.152345797C>T
NG_027988.1:g.32454G>A
NM_005431.1:c.773G>A

Protein change:

R258H

Links:

dbSNP: rs149186933

Molecular consequence:

NM_005431.2:c.773G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000675845	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Jan 9, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28779002, 28912153 Citation Link,
SCV002538381	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Jan 9, 2022)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000675845

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Jan 9, 2024)

germline

clinical testing

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

Citation Link,

SCV002538381

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Jan 9, 2022)

germline

curation

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

Citation Link

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	clinical testing, curation

Citations

PubMed

Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.

Decker B, Allen J, Luccarini C, Pooley KA, Shah M, Bolla MK, Wang Q, Ahmed S, Baynes C, Conroy DM, Brown J, Luben R, Ostrander EA, Pharoah PD, Dunning AM, Easton DF.

J Med Genet. 2017 Nov;54(11):732-741. doi: 10.1136/jmedgenet-2017-104588. Epub 2017 Aug 4.

PubMed [citation]

PMID:: 28779002
PMCID:: PMC5740532

Comprehensive Genomic Profiling of 282 Pediatric Low- and High-Grade Gliomas Reveals Genomic Drivers, Tumor Mutational Burden, and Hypermutation Signatures.

Johnson A, Severson E, Gay L, Vergilio JA, Elvin J, Suh J, Daniel S, Covert M, Frampton GM, Hsu S, Lesser GJ, Stogner-Underwood K, Mott RT, Rush SZ, Stanke JJ, Dahiya S, Sun J, Reddy P, Chalmers ZR, Erlich R, Chudnovsky Y, Fabrizio D, et al.

Oncologist. 2017 Dec;22(12):1478-1490. doi: 10.1634/theoncologist.2017-0242. Epub 2017 Sep 14.

PubMed [citation]

PMID:: 28912153
PMCID:: PMC5728033

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000675845.5

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 Sema4, Sema4, SCV002538381.1

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

#	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: Apr 12, 2026

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