6-31935989-AT-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000063.6(C2):c.917delT(p.Met306SerfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000063.6 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
C2 | ENST00000299367.10 | c.917delT | p.Met306SerfsTer4 | frameshift_variant | Exon 7 of 18 | 1 | NM_000063.6 | ENSP00000299367.5 | ||
ENSG00000244255 | ENST00000456570.5 | c.530-1329delT | intron_variant | Intron 4 of 29 | 2 | ENSP00000410815.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not provided Pathogenic:1
This variant has not been reported in the literature in individuals affected with C2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Met306Serfs*4) in the C2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in C2 are known to be pathogenic (PMID: 1577763, 9616367). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.