rs764884250
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001035.3(RYR2):āc.13195A>Gā(p.Asn4399Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,611,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001035.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RYR2 | NM_001035.3 | c.13195A>G | p.Asn4399Asp | missense_variant | 90/105 | ENST00000366574.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RYR2 | ENST00000366574.7 | c.13195A>G | p.Asn4399Asp | missense_variant | 90/105 | 1 | NM_001035.3 | P1 | |
RYR2 | ENST00000660292.2 | c.13216A>G | p.Asn4406Asp | missense_variant | 91/106 | ||||
RYR2 | ENST00000659194.3 | c.13183A>G | p.Asn4395Asp | missense_variant | 90/105 | ||||
RYR2 | ENST00000609119.2 | c.*4287A>G | 3_prime_UTR_variant, NMD_transcript_variant | 89/104 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152112Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000124 AC: 3AN: 242380Hom.: 0 AF XY: 0.00000760 AC XY: 1AN XY: 131496
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459122Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2AN XY: 725566
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152112Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74306
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 03, 2023 | The p.N4399D variant (also known as c.13195A>G), located in coding exon 90 of the RYR2 gene, results from an A to G substitution at nucleotide position 13195. The asparagine at codon 4399 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at