chr20-44186291-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020433.5(JPH2):c.379+36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 1,604,436 control chromosomes in the GnomAD database, including 561,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 56211 hom., cov: 27)

Exomes 𝑓: 0.83 ( 505623 hom. )

Consequence

JPH2
NM_020433.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.491

Publications

7 publications found

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 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

JPH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 20-44186291-T-C is Benign according to our data. Variant chr20-44186291-T-C is described in ClinVar as [Benign]. Clinvar id is 671113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
JPH2	NM_020433.5 link	c.379+36A>G	intron_variant	Intron 1 of 5	ENST00000372980.4	NP_065166.2	Q9BR39-1Q86VZ3
JPH2	NM_175913.4 link	c.379+36A>G	intron_variant	Intron 1 of 1		NP_787109.2	Q9BR39-2
JPH2	XM_006723833.5 link	c.379+36A>G	intron_variant	Intron 1 of 1		XP_006723896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JPH2	ENST00000372980.4 link	c.379+36A>G		intron_variant	Intron 1 of 5	5	NM_020433.5	ENSP00000362071.3		Q9BR39-1
JPH2	ENST00000342272.3 link	c.379+36A>G		intron_variant	Intron 1 of 1	1		ENSP00000344590.3		Q9BR39-2

Frequencies

GnomAD3 genomes

AF:

0.860

AC:

130244

AN:

151422

Hom.:

56157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.928

Gnomad AMI

AF:

0.726

Gnomad AMR

AF:

0.869

Gnomad ASJ

AF:

0.824

Gnomad EAS

AF:

0.832

Gnomad SAS

AF:

0.833

Gnomad FIN

AF:

0.836

Gnomad MID

AF:

0.818

Gnomad NFE

AF:

0.828

Gnomad OTH

AF:

0.862

GnomAD2 exomes

AF:

0.847

AC:

206046

AN:

243244

AF XY:

0.842

show subpopulations

Gnomad AFR exome

AF:

0.931

Gnomad AMR exome

AF:

0.907

Gnomad ASJ exome

AF:

0.832

Gnomad EAS exome

AF:

0.828

Gnomad FIN exome

AF:

0.839

Gnomad NFE exome

AF:

0.824

Gnomad OTH exome

AF:

0.837

GnomAD4 exome

AF:

0.834

AC:

1211015

AN:

1452896

Hom.:

505623

Cov.:

AF XY:

0.833

AC XY:

602277

AN XY:

723012

show subpopulations

African (AFR)

AF:

0.927

AC:

30944

AN:

33372

American (AMR)

AF:

0.903

AC:

40199

AN:

44512

Ashkenazi Jewish (ASJ)

AF:

0.835

AC:

21721

AN:

26010

East Asian (EAS)

AF:

0.877

AC:

34814

AN:

39692

South Asian (SAS)

AF:

0.846

AC:

72848

AN:

86100

European-Finnish (FIN)

AF:

0.835

AC:

39114

AN:

46816

Middle Eastern (MID)

AF:

0.845

AC:

4831

AN:

5716

European-Non Finnish (NFE)

AF:

0.825

AC:

916279

AN:

1110416

Other (OTH)

AF:

0.834

AC:

50265

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

10458

20915

31373

41830

52288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.860

AC:

130358

AN:

151540

Hom.:

56211

Cov.:

AF XY:

0.860

AC XY:

63694

AN XY:

74030

show subpopulations

African (AFR)

AF:

0.928

AC:

38308

AN:

41268

American (AMR)

AF:

0.869

AC:

13256

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.824

AC:

2858

AN:

3468

East Asian (EAS)

AF:

0.832

AC:

4208

AN:

5058

South Asian (SAS)

AF:

0.834

AC:

3992

AN:

4786

European-Finnish (FIN)

AF:

0.836

AC:

8820

AN:

10544

Middle Eastern (MID)

AF:

0.815

AC:

238

AN:

292

European-Non Finnish (NFE)

AF:

0.828

AC:

56203

AN:

67858

Other (OTH)

AF:

0.862

AC:

1816

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

892

1783

2675

3566

4458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.847

Hom.:

10298

Bravo

AF:

0.865

Asia WGS

AF:

0.829

AC:

2884

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.1

(source)

DANN

Benign

0.32

PhyloP100

-0.49

Mutation Taster

=16/84

disease causing

(source)

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

Publications

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chr20-44186291-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over