chr7-152648641-ATCAACAAAAT-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_005431.2(XRCC2):c.834_843del(p.Glu278AspfsTer16) variant causes a frameshift, stop lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. E278E) has been classified as Likely benign.
Frequency
Consequence
NM_005431.2 frameshift, stop_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XRCC2 | NM_005431.2 | c.834_843del | p.Glu278AspfsTer16 | frameshift_variant, stop_lost | 3/3 | ENST00000359321.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XRCC2 | ENST00000359321.2 | c.834_843del | p.Glu278AspfsTer16 | frameshift_variant, stop_lost | 3/3 | 1 | NM_005431.2 | P1 | |
XRCC2 | ENST00000495707.1 | n.856_865del | non_coding_transcript_exon_variant | 3/3 | 1 | ||||
XRCC2 | ENST00000698506.1 | c.666_675del | p.Glu222AspfsTer16 | frameshift_variant, stop_lost | 2/2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 13, 2023 | 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 and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1762998). This variant has not been reported in the literature in individuals affected with XRCC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the XRCC2 gene (p.Glu278Aspfs*16). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 3 amino acid(s) of the XRCC2 protein and extend the protein by 12 additional amino acid residues. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 12, 2023 | The c.834_843del10 variant, located in coding exon 3 of the XRCC2 gene, results from a deletion of 10 nucleotides at nucleotide positions 834 to 843, causing a translational frameshift with a predicted alternate stop codon (p.E278Dfs*16). This alteration occurs at the 3' terminus of theXRCC2 gene, is not expected to trigger nonsense-mediated mRNAdecay and results in the elongation of the protein by 12 amino acids. This frameshift impacts the last 3amino acids of the native protein. The exact functional effect of the altered amino acids is unknown. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.