rs6073358

Variant names:

• chr20-44174096-C-T
• rs6073358
• NM_020433.5:c.379+12231G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020433.5(JPH2):​c.379+12231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 152,254 control chromosomes in the GnomAD database, including 548 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.077 (548 hom., cov: 32)
• Consequence: JPH2 NM_020433.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 2 publications found

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]

JPH2 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy 17

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• cardiomyopathy, dilated, 2E

  Inheritance: Unknown, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• dilated cardiomyopathy

  Inheritance: SD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JPH2	NM_020433.5	c.379+12231G>A		intron_variant	Intron 1 of 5	ENST00000372980.4	NP_065166.2
JPH2	XM_006723833.5	c.*7410G>A		3_prime_UTR_variant	Exon 2 of 2		XP_006723896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JPH2	ENST00000372980.4	c.379+12231G>A		intron_variant	Intron 1 of 5	5	NM_020433.5	ENSP00000362071.3

Frequencies

GnomAD3 genomes AF: 0.0771 AC: 11731 AN: 152134 Hom.: 546 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0935

Gnomad OTH AF: 0.0887

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0771 AC: 11737 AN: 152254 Hom.: 548 Cov.: 32 AF XY: 0.0807 AC XY: 6003 AN XY: 74432

African (AFR) AF: 0.0303 AC: 1259 AN: 41550

American (AMR) AF: 0.0813 AC: 1244 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3470

East Asian (EAS) AF: 0.0179 AC: 93 AN: 5188

South Asian (SAS) AF: 0.101 AC: 486 AN: 4824

European-Finnish (FIN) AF: 0.166 AC: 1758 AN: 10588

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0935 AC: 6362 AN: 68026

Other (OTH) AF: 0.0877 AC: 185 AN: 2110

Alfa AF: 0.0859 Hom.: 1834

Bravo AF: 0.0691

Asia WGS AF: 0.0650 AC: 225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.54
PhyloP100		-0.067
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6073358; hg19: chr20-42802736;