chr20-44160007-G-A
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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.780C>T(p.Ala260=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000382 in 1,573,500 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00037 ( 7 hom. )
Consequence
JPH2
NM_020433.5 synonymous
NM_020433.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.129
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=-0.55).
BP6
Variant 20-44160007-G-A is Benign according to our data. Variant chr20-44160007-G-A is described in ClinVar as [Benign]. Clinvar id is 226677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-44160007-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.129 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000467 (71/152144) while in subpopulation EAS AF= 0.0136 (70/5140). AF 95% confidence interval is 0.0111. There are 0 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 7 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JPH2 | NM_020433.5 | c.780C>T | p.Ala260= | synonymous_variant | 2/6 | ENST00000372980.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JPH2 | ENST00000372980.4 | c.780C>T | p.Ala260= | synonymous_variant | 2/6 | 5 | NM_020433.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000467 AC: 71AN: 152030Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00126 AC: 232AN: 184154Hom.: 4 AF XY: 0.00128 AC XY: 128AN XY: 100348
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GnomAD4 exome AF: 0.000373 AC: 530AN: 1421356Hom.: 7 Cov.: 32 AF XY: 0.000386 AC XY: 272AN XY: 704680
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GnomAD4 genome AF: 0.000467 AC: 71AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34AN XY: 74370
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 25, 2015 | p.Ala260Ala in exon 2 of JPH2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 3.5% (73/2104) of Eas t Asian chromosomes, including 3 homozygotes, by the Exome Aggregation Consortiu m (ExAC, http://exac.broadinstitute.org; dbSNP rs199840543). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 16, 2015 | 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. - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Hypertrophic cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 11, 2016 | This alteration is classified as 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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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at