rs778410296
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020433.5(JPH2):āc.1951A>Gā(p.Lys651Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_020433.5 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 |
---|---|---|---|---|---|---|---|---|
JPH2 | NM_020433.5 | c.1951A>G | p.Lys651Glu | missense_variant | 4/6 | ENST00000372980.4 | NP_065166.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
JPH2 | ENST00000372980.4 | c.1951A>G | p.Lys651Glu | missense_variant | 4/6 | 5 | NM_020433.5 | ENSP00000362071 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000162 AC: 4AN: 246302Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133258
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461248Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 726948
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74360
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 16, 2015 | The p.Lys651Glu variant in JPH2 has not been previously reported in individuals with cardiomyopathy, but been identified in 1/11412 Latino chromosomes by the Ex ome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Lys651Glu variant is uncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 22, 2022 | This variant is present in population databases (rs778410296, gnomAD 0.009%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 191668). This variant has not been reported in the literature in individuals affected with JPH2-related conditions. This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 651 of the JPH2 protein (p.Lys651Glu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at