rs1883790

Variant names:

• chr20-44186550-G-A
• rs1883790
• NM_020433.5:c.156C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020433.5(JPH2):​c.156C>T​(p.Tyr52Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 1,613,862 control chromosomes in the GnomAD database, including 565,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (56829 hom., cov: 31)
  • Exomes 𝑓: 0.83 (508580 hom.)
• Consequence: JPH2 NM_020433.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: 2.27
• Publications: 22 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 Submitted by: Labcorp Genetics (formerly Invitae)
• dilated cardiomyopathy

  Inheritance: SD, AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: ClinGen
• 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 20-44186550-G-A is Benign according to our data. Variant chr20-44186550-G-A is described in ClinVar as Benign. ClinVar VariationId is 137602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020433.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH2	NM_020433.5	MANE Select	c.156C>T	p.Tyr52Tyr	synonymous	Exon 1 of 6	NP_065166.2
	JPH2	NM_175913.4		c.156C>T	p.Tyr52Tyr	synonymous	Exon 1 of 2	NP_787109.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH2	ENST00000372980.4	TSL:5 MANE Select	c.156C>T	p.Tyr52Tyr	synonymous	Exon 1 of 6	ENSP00000362071.3	Q9BR39-1
	JPH2	ENST00000342272.3	TSL:1	c.156C>T	p.Tyr52Tyr	synonymous	Exon 1 of 2	ENSP00000344590.3	Q9BR39-2
	JPH2	ENST00000900331.1		c.156C>T	p.Tyr52Tyr	synonymous	Exon 1 of 7	ENSP00000570390.1

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131113 AN: 151972 Hom.: 56769 Cov.: 31

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.864

GnomAD2 exomes AF: 0.846 AC: 212362 AN: 251152 AF XY: 0.840

Gnomad AFR exome AF: 0.939

Gnomad AMR exome AF: 0.915

Gnomad ASJ exome AF: 0.845

Gnomad EAS exome AF: 0.748

Gnomad FIN exome AF: 0.847

Gnomad NFE exome AF: 0.829

Gnomad OTH exome AF: 0.838

GnomAD4 exome AF: 0.833 AC: 1218304 AN: 1461772 Hom.: 508580 Cov.: 74 AF XY: 0.833 AC XY: 605477 AN XY: 727178

African (AFR) AF: 0.936 AC: 31336 AN: 33478

American (AMR) AF: 0.911 AC: 40751 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 22133 AN: 26134

East Asian (EAS) AF: 0.743 AC: 29502 AN: 39698

South Asian (SAS) AF: 0.839 AC: 72377 AN: 86258

European-Finnish (FIN) AF: 0.843 AC: 44976 AN: 53360

Middle Eastern (MID) AF: 0.835 AC: 4814 AN: 5768

European-Non Finnish (NFE) AF: 0.829 AC: 921950 AN: 1111962

Other (OTH) AF: 0.836 AC: 50465 AN: 60390

GnomAD4 genome AF: 0.863 AC: 131234 AN: 152090 Hom.: 56829 Cov.: 31 AF XY: 0.863 AC XY: 64140 AN XY: 74346

African (AFR) AF: 0.936 AC: 38849 AN: 41518

American (AMR) AF: 0.877 AC: 13412 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2898 AN: 3470

East Asian (EAS) AF: 0.751 AC: 3845 AN: 5120

South Asian (SAS) AF: 0.831 AC: 4012 AN: 4826

European-Finnish (FIN) AF: 0.839 AC: 8894 AN: 10596

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.833 AC: 56602 AN: 67958

Other (OTH) AF: 0.864 AC: 1822 AN: 2108

Alfa AF: 0.844 Hom.: 85894

Bravo AF: 0.867

Asia WGS AF: 0.815 AC: 2834 AN: 3478

EpiCase AF: 0.832

EpiControl AF: 0.822

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	Hypertrophic cardiomyopathy 17 (3)
-	-	2	not provided (2)
-	-	1	Cardiomyopathy, dilated, 2E (1)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Hypertrophic cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.6
DANN	Benign	0.52
PhyloP100		2.3
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: rs1883790; hg19: chr20-42815190; COSMIC: COSV60697412;