chr9-2717759-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_133497.4(KCNV2):c.20G>A(p.Arg7Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7M) has been classified as Uncertain significance.
Frequency
Consequence
NM_133497.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNV2 | NM_133497.4 | c.20G>A | p.Arg7Lys | missense_variant | 1/2 | ENST00000382082.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNV2 | ENST00000382082.4 | c.20G>A | p.Arg7Lys | missense_variant | 1/2 | 1 | NM_133497.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152208Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461878Hom.: 0 Cov.: 68 AF XY: 0.00000825 AC XY: 6AN XY: 727242
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74364
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | This variant has not been reported in the literature in individuals affected with KCNV2-related conditions. This variant is present in population databases (rs370186140, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 7 of the KCNV2 protein (p.Arg7Lys). ClinVar contains an entry for this variant (Variation ID: 970650). 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 have shown that this missense change affects KCNV2 function (PMID: 21402906). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KCNV2 protein function. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at