rs1131692244
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_020433.5(JPH2):c.278G>A(p.Arg93His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R93C) has been classified as Uncertain significance.
Frequency
Consequence
NM_020433.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JPH2 | NM_020433.5 | c.278G>A | p.Arg93His | missense_variant | 1/6 | ENST00000372980.4 | |
JPH2 | NM_175913.4 | c.278G>A | p.Arg93His | missense_variant | 1/2 | ||
JPH2 | XM_006723833.5 | c.278G>A | p.Arg93His | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JPH2 | ENST00000372980.4 | c.278G>A | p.Arg93His | missense_variant | 1/6 | 5 | NM_020433.5 | P1 | |
JPH2 | ENST00000342272.3 | c.278G>A | p.Arg93His | missense_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250994Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135620
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461740Hom.: 0 Cov.: 65 AF XY: 0.00000963 AC XY: 7AN XY: 727180
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 04, 2017 | A variant of uncertain significance has been identified in the JPH2 gene. The R93H variant has not been published as pathogenic or been reported as benign to our knowledge. The R93H variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R93H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | JPH2: PM2 - |
Hypertrophic cardiomyopathy 17;C5561970:Cardiomyopathy, dilated, 2E Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 09, 2022 | - - |
Primary dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Institute Of Molecular Biology And Genetics, Federal Almazov National Medical Research Centre | - | The patients has dilated cardiomyopathy with predominant right ventricular dilation diagnosed at age of 16. No arrhythmia or other criteria of ARVC are observed. The mutation is inherited from the mother who has areas of myocardial fibrosis, akinesia and slightly reduced systolic function without prior myocardial infarction of other causes at the of 45. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at