Genetic Variant JPH2:c.*14+209_*14+216delACACACAC (chr20-44114565-AGTGTGTGT-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_020433.5(JPH2):c.*14+209_*14+216delACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.23 ( 4010 hom., cov: 0)

Consequence

JPH2
NM_020433.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.794

Publications

0 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 -10 ACMG points.

BP6

Variant 20-44114565-AGTGTGTGT-A is Benign according to our data. Variant chr20-44114565-AGTGTGTGT-A is described in ClinVar as [Benign]. Clinvar id is 1265714.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JPH2	NM_020433.5 link	c.14+209_14+216delACACACAC		intron_variant	Intron 5 of 5	ENST00000372980.4	NP_065166.2	Q9BR39-1Q86VZ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JPH2	ENST00000372980.4 link	c.14+209_14+216delACACACAC		intron_variant	Intron 5 of 5	5	NM_020433.5	ENSP00000362071.3		Q9BR39-1

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

32617

AN:

141676

Hom.:

4010

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.0673

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.188

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.227

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

GnomAD4 genome

AF:

0.230

AC:

32635

AN:

141774

Hom.:

4010

Cov.:

AF XY:

0.230

AC XY:

15676

AN XY:

68276

show subpopulations

African (AFR)

AF:

0.134

AC:

5125

AN:

38248

American (AMR)

AF:

0.210

AC:

2965

AN:

14146

Ashkenazi Jewish (ASJ)

AF:

0.317

AC:

1062

AN:

3348

East Asian (EAS)

AF:

0.0677

AC:

312

AN:

4608

South Asian (SAS)

AF:

0.216

AC:

879

AN:

4066

European-Finnish (FIN)

AF:

0.305

AC:

2754

AN:

9026

Middle Eastern (MID)

AF:

0.200

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.289

AC:

18840

AN:

65216

Other (OTH)

AF:

0.225

AC:

442

AN:

1968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1086

2172

3258

4344

5430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.277

Hom.:

238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 06, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.79

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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chr20-44114565-AGTGTGTGT-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over