rs753383507
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_020433.5(JPH2):c.1758G>A(p.Glu586=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000955 in 1,571,366 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000092 ( 0 hom. )
Consequence
JPH2
NM_020433.5 synonymous
NM_020433.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0160
Genes affected
JPH2 (HGNC:14202): (junctophilin 2) Junctional complexes between the plasma membrane and endoplasmic/sarcoplasmic reticulum are a common feature of all excitable cell types and mediate cross talk between cell surface and intracellular ion channels. The protein encoded by this gene is a component of junctional complexes and is composed of a C-terminal hydrophobic segment spanning the endoplasmic/sarcoplasmic reticulum membrane and a remaining cytoplasmic domain that shows specific affinity for the plasma membrane. This gene is a member of the junctophilin gene family. Alternative splicing has been observed at this locus and two variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 20-44115917-C-T is Benign according to our data. Variant chr20-44115917-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 520524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.016 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JPH2 | NM_020433.5 | c.1758G>A | p.Glu586= | synonymous_variant | 4/6 | ENST00000372980.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JPH2 | ENST00000372980.4 | c.1758G>A | p.Glu586= | synonymous_variant | 4/6 | 5 | NM_020433.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152144Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000397 AC: 7AN: 176490Hom.: 0 AF XY: 0.0000407 AC XY: 4AN XY: 98378
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GnomAD4 exome AF: 0.00000916 AC: 13AN: 1419222Hom.: 0 Cov.: 33 AF XY: 0.0000142 AC XY: 10AN XY: 703808
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152144Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74310
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | Jun 22, 2017 | - - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 12, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at