rs200892606
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_020433.5(JPH2):c.1704C>T(p.Ser568=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000272 in 1,576,722 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00045 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00025 ( 2 hom. )
Consequence
JPH2
NM_020433.5 synonymous
NM_020433.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.20
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 20-44115971-G-A is Benign according to our data. Variant chr20-44115971-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 215527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-44115971-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=2.2 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000447 (68/152268) while in subpopulation NFE AF= 0.000118 (8/68000). AF 95% confidence interval is 0.0000584. There are 1 homozygotes in gnomad4. There are 47 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 2 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JPH2 | NM_020433.5 | c.1704C>T | p.Ser568= | synonymous_variant | 4/6 | ENST00000372980.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JPH2 | ENST00000372980.4 | c.1704C>T | p.Ser568= | synonymous_variant | 4/6 | 5 | NM_020433.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000447 AC: 68AN: 152160Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000369 AC: 68AN: 184092Hom.: 2 AF XY: 0.000312 AC XY: 32AN XY: 102466
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GnomAD4 exome AF: 0.000253 AC: 361AN: 1424454Hom.: 2 Cov.: 34 AF XY: 0.000218 AC XY: 154AN XY: 707056
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GnomAD4 genome ? AF: 0.000447 AC: 68AN: 152268Hom.: 1 Cov.: 32 AF XY: 0.000631 AC XY: 47AN XY: 74446
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 10, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Hypertrophic cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 05, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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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