rs1060500146
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001035.3(RYR2):āc.4238A>Gā(p.Asp1413Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,324 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1413V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001035.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR2 | NM_001035.3 | c.4238A>G | p.Asp1413Gly | missense_variant | 32/105 | ENST00000366574.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR2 | ENST00000366574.7 | c.4238A>G | p.Asp1413Gly | missense_variant | 32/105 | 1 | NM_001035.3 | P1 | |
RYR2 | ENST00000660292.2 | c.4238A>G | p.Asp1413Gly | missense_variant | 32/106 | ||||
RYR2 | ENST00000659194.3 | c.4238A>G | p.Asp1413Gly | missense_variant | 32/105 | ||||
RYR2 | ENST00000609119.2 | c.4238A>G | p.Asp1413Gly | missense_variant, NMD_transcript_variant | 32/104 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461324Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726920
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Catecholaminergic polymorphic ventricular tachycardia 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 21, 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. 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 RYR2 protein function. This variant has not been reported in the literature in individuals with RYR2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glycine at codon 1413 of the RYR2 protein (p.Asp1413Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at