rs6073330

Variant names:

• chr20-44108854-C-A
• rs6073330
• NM_020433.5:c.*4664G>T

Variant summary

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

The NM_020433.5(JPH2):​c.*4664G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,868 control chromosomes in the GnomAD database, including 6,849 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 0.29 (6849 hom., cov: 31)
• Consequence: JPH2 NM_020433.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JPH2	NM_020433.5	c.*4664G>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000372980.4	NP_065166.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JPH2	ENST00000372980.4	c.*4664G>T		3_prime_UTR_variant	Exon 6 of 6	5	NM_020433.5	ENSP00000362071.3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44550 AN: 151750 Hom.: 6840 Cov.: 31

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.294 AC: 44591 AN: 151868 Hom.: 6849 Cov.: 31 AF XY: 0.295 AC XY: 21900 AN XY: 74244

African (AFR) AF: 0.326 AC: 13488 AN: 41380

American (AMR) AF: 0.307 AC: 4677 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 847 AN: 3468

East Asian (EAS) AF: 0.472 AC: 2423 AN: 5138

South Asian (SAS) AF: 0.450 AC: 2163 AN: 4812

European-Finnish (FIN) AF: 0.224 AC: 2366 AN: 10570

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17684 AN: 67930

Other (OTH) AF: 0.291 AC: 614 AN: 2108

Alfa AF: 0.277 Hom.: 19188

Bravo AF: 0.302

Asia WGS AF: 0.452 AC: 1571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.80
PhyloP100		-0.68

Splicing

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

Other links and lift over

dbSNP: rs6073330; hg19: chr20-42737494;