6-31936014-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000063.6(C2):c.941G>A(p.Arg314Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,612,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000063.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
C2 | NM_000063.6 | c.941G>A | p.Arg314Gln | missense_variant | 7/18 | ENST00000299367.10 | NP_000054.2 | |
C2-AS1 | NR_104191.1 | n.541-612C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
C2 | ENST00000299367.10 | c.941G>A | p.Arg314Gln | missense_variant | 7/18 | 1 | NM_000063.6 | ENSP00000299367 | P1 | |
C2-AS1 | ENST00000630806.1 | n.541-612C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246642Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134434
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1460768Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 726704
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152110Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74300
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 17, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 1460531). This variant has not been reported in the literature in individuals affected with C2-related conditions. This variant is present in population databases (rs550498736, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 314 of the C2 protein (p.Arg314Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at