NM_005431.2(XRCC2):c.350dup (p.Leu117fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 1, 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:: RCV002455921.3

Allele description [Variation Report for NM_005431.2(XRCC2):c.350dup (p.Leu117fs)]

NM_005431.2(XRCC2):c.350dup (p.Leu117fs)

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.350dup (p.Leu117fs)

HGVS:

NC_000007.14:g.152649142dup
NG_027988.2:g.32031dup
NM_005431.2:c.350dupMANE SELECT
NP_005422.1:p.Leu117fs
LRG_323t1:c.350dup
LRG_323:g.32031dup
LRG_323p1:p.Leu117fs
NC_000007.13:g.152346219_152346220insA
NC_000007.13:g.152346227dup
NG_027988.1:g.32031dup
NM_005431.1:c.350dup
NM_005431.1:c.350dupT

Protein change:

L117fs

Links:

dbSNP: rs764640893

NCBI 1000 Genomes Browser:

rs764640893

Molecular consequence:

NM_005431.2:c.350dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV002613061	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (May 1, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002613061

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(May 1, 2023)

germline

clinical testing

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

Details of each submission

From Ambry Genetics, SCV002613061.3

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

Description

The c.350dupT variant, located in coding exon 3 of the XRCC2 gene, results from a duplication of T at nucleotide position 350, causing a translational frameshift with a predicted alternate stop codon (p.L117Ffs*6). This alteration occurs at the 3' terminus of the XRCC2 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 164 amino acids of the protein. However, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	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: Sep 29, 2024

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