NM_005431.2(XRCC2):c.677dup (p.Tyr226Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 29, 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:: RCV003307419.2

Allele description [Variation Report for NM_005431.2(XRCC2):c.677dup (p.Tyr226Ter)]

NM_005431.2(XRCC2):c.677dup (p.Tyr226Ter)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

7q36.1

Genomic location:

Preferred name:

NM_005431.2(XRCC2):c.677dup (p.Tyr226Ter)

HGVS:

NC_000007.14:g.152648808dup
NG_027988.2:g.32358dup
NM_005431.1:c.677dupA
NM_005431.2:c.677dupMANE SELECT
NP_005422.1:p.Tyr226Ter
LRG_323t1:c.677dup
LRG_323:g.32358dup
LRG_323p1:p.Tyr226Ter
NC_000007.13:g.152345893dup
NG_027988.1:g.32358dup
NM_005431.2:c.677dupAMANE SELECT

Protein change:

Y226*

Links:

dbSNP: rs1590129294

NCBI 1000 Genomes Browser:

rs1590129294

Molecular consequence:

NM_005431.2:c.677dup - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004000816	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 29, 2023)	germline	clinical testing	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

SCV004000816

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 29, 2023)

germline

clinical testing

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

Citations

PubMed

Contribution of germline deleterious variants in the RAD51 paralogs to breast and ovarian cancers.

Golmard L, Castéra L, Krieger S, Moncoutier V, Abidallah K, Tenreiro H, Laugé A, Tarabeux J, Millot GA, Nicolas A, Laé M, Abadie C, Berthet P, Polycarpe F, Frébourg T, Elan C, de Pauw A, Gauthier-Villars M, Buecher B, Stern MH, Stoppa-Lyonnet D, Vaur D, et al.

Eur J Hum Genet. 2017 Dec;25(12):1345-1353. doi: 10.1038/s41431-017-0021-2. Epub 2017 Nov 8.

PubMed [citation]

PMID:: 29255180
PMCID:: PMC5865182

Details of each submission

From Ambry Genetics, SCV004000816.2

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

Description

The c.677dupA variant, located in coding exon 3 of the XRCC2 gene, results from a duplication of A at nucleotide position 677, causing a translational frameshift with a predicted alternate stop codon (p.Y226*). This alteration occurs at the 3' terminus of theXRCC2 gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 55 amino acids of the protein. The exact functional effect of this alteration is unknown. This variant was identified in a hereditary breast and ovarian cancer cohort (Golmard L et al. Eur J Hum Genet, 2017 Dec;25:1345-1353). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Jul 15, 2024

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