rs1327414828
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_005431.2(XRCC2):āc.223G>Cā(p.Glu75Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E75K) has been classified as Uncertain significance.
Frequency
Consequence
NM_005431.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XRCC2 | NM_005431.2 | c.223G>C | p.Glu75Gln | missense_variant | 3/3 | ENST00000359321.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XRCC2 | ENST00000359321.2 | c.223G>C | p.Glu75Gln | missense_variant | 3/3 | 1 | NM_005431.2 | P1 | |
XRCC2 | ENST00000495707.1 | n.245G>C | non_coding_transcript_exon_variant | 3/3 | 1 | ||||
XRCC2 | ENST00000698506.1 | c.55G>C | p.Glu19Gln | missense_variant | 2/2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250842Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135670
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461492Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727042
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 01, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies in a cell line have shown that this missense change does not impair XRCC2 protein function (PMID: 27233470). This variant has been reported in an individual affected with breast cancer (PMID: 23054243). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glutamine at codon 75 of the XRCC2 protein (p.Glu75Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. - |
not specified Benign:1
Likely benign, no assertion criteria provided | curation | Leiden Open Variation Database | Mar 01, 2013 | Curator: Arleen D. Auerbach. Submitter to LOVD: Florentine Hilbers. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 28, 2019 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at