rs1060502667
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PVS1_Moderate
The NM_005431.2(XRCC2):c.789_790del(p.Asn263LysfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. N263N) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
XRCC2
NM_005431.2 frameshift
NM_005431.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.15
Genes affected
XRCC2 (HGNC:12829): (X-ray repair cross complementing 2) This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene is involved in the repair of DNA double-strand breaks by homologous recombination and it functionally complements Chinese hamster irs1, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0641 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XRCC2 | NM_005431.2 | c.789_790del | p.Asn263LysfsTer15 | frameshift_variant | 3/3 | ENST00000359321.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XRCC2 | ENST00000359321.2 | c.789_790del | p.Asn263LysfsTer15 | frameshift_variant | 3/3 | 1 | NM_005431.2 | P1 | |
XRCC2 | ENST00000495707.1 | n.811_812del | non_coding_transcript_exon_variant | 3/3 | 1 | ||||
XRCC2 | ENST00000698506.1 | c.621_622del | p.Asn207LysfsTer15 | frameshift_variant | 2/2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 03, 2016 | Experimental studies have not been reported for this variant and it is currently unknown if the last 18 amino acids of the XRCC2 protein are critical for its function. This sequence change deletes 2 nucleotides from exon 3 of the XRCC2 mRNA (c.789_790delCA), causing a frameshift at codon 263. This creates a premature translational stop signal in the last exon of the XRCC2 mRNA (p.Asn263Lysfs*15). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 18 amino acids of the XRCC2 protein. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in XRCC2 cause disease. Therefore, this variant has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a XRCC2-related disease. - |
Computational scores
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at