20-44160416-G-C

Position:

chr20-44160416-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020433.5(JPH2):c.380-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,608,122 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 22 hom. )

Consequence

JPH2
NM_020433.5 intron

Scores

Splicing: ADA: 0.00007931

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.421

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 20-44160416-G-C is Benign according to our data. Variant chr20-44160416-G-C is described in ClinVar as [Benign]. Clinvar id is 137603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-44160416-G-C is described in Lovd as [Benign]. Variant chr20-44160416-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00411 (627/152370) while in subpopulation NFE AF= 0.00459 (312/68042). AF 95% confidence interval is 0.00417. There are 2 homozygotes in gnomad4. There are 359 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JPH2	NM_020433.5 linkuse as main transcript	c.380-9C>G		intron_variant		ENST00000372980.4	NP_065166.2	Q9BR39-1Q86VZ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JPH2	ENST00000372980.4 linkuse as main transcript	c.380-9C>G		intron_variant		5	NM_020433.5	ENSP00000362071.3		Q9BR39-1

Frequencies

GnomAD3 genomes

AF:

0.00412

AC:

627

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0206

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00458

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00438

AC:

1018

AN:

232644

Hom.:

AF XY:

0.00432

AC XY:

552

AN XY:

127698

show subpopulations

Gnomad AFR exome

AF:

0.000357

Gnomad AMR exome

AF:

0.000977

Gnomad ASJ exome

AF:

0.00618

Gnomad EAS exome

AF:

0.0000571

Gnomad SAS exome

AF:

0.00110

Gnomad FIN exome

AF:

0.0202

Gnomad NFE exome

AF:

0.00448

Gnomad OTH exome

AF:

0.00517

GnomAD4 exome

AF:

0.00398

AC:

5787

AN:

1455752

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

2923

AN XY:

723876

show subpopulations

Gnomad4 AFR exome

AF:

0.000270

Gnomad4 AMR exome

AF:

0.00104

Gnomad4 ASJ exome

AF:

0.00628

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00147

Gnomad4 FIN exome

AF:

0.0178

Gnomad4 NFE exome

AF:

0.00389

Gnomad4 OTH exome

AF:

0.00318

GnomAD4 genome

AF:

0.00411

AC:

627

AN:

152370

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

359

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00300

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0206

Gnomad4 NFE

AF:

0.00459

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00437

Hom.:

Bravo

AF:

0.00282

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 01, 2015	c.380-9C>G in intron 1 of JPH2: This variant is not expected to have clinical si gnificance because it has been identified in 2.9% (78/2666) of Finnish chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs111987307). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 06, 2014	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:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 15, 2022	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Hypertrophic cardiomyopathy 17

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.3

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000079

dbscSNV1_RF

Benign

0.048

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over