20-44114565-AGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant names:

• chr20-44114565-A-AGT
• rs3037626
• NM_020433.5:c.*14+215_*14+216dupAC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020433.5(JPH2):​c.*14+215_*14+216dupAC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.039 (123 hom., cov: 0)
• Consequence: JPH2 NM_020433.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.794
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 20-44114565-A-AGT is Benign according to our data. Variant chr20-44114565-A-AGT is described in ClinVar as [Benign]. Clinvar id is 1246902.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.05 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JPH2	NM_020433.5	c.*14+215_*14+216dupAC		intron_variant	Intron 5 of 5	ENST00000372980.4	NP_065166.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JPH2	ENST00000372980.4	c.*14+216_*14+217insAC		intron_variant	Intron 5 of 5	5	NM_020433.5	ENSP00000362071.3

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5568 AN: 141784 Hom.: 123 Cov.: 0

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.0522

Gnomad SAS AF: 0.0558

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.0651

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0345

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

GnomAD4 genome AF: 0.0393 AC: 5572 AN: 141882 Hom.: 123 Cov.: 0 AF XY: 0.0404 AC XY: 2761 AN XY: 68330

African (AFR) AF: 0.0189 AC: 724 AN: 38288

American (AMR) AF: 0.0497 AC: 704 AN: 14156

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 155 AN: 3344

East Asian (EAS) AF: 0.0521 AC: 240 AN: 4604

South Asian (SAS) AF: 0.0560 AC: 228 AN: 4074

European-Finnish (FIN) AF: 0.0573 AC: 518 AN: 9040

Middle Eastern (MID) AF: 0.0593 AC: 16 AN: 270

European-Non Finnish (NFE) AF: 0.0442 AC: 2884 AN: 65260

Other (OTH) AF: 0.0362 AC: 71 AN: 1964

Alfa AF: 0.0401 Hom.: 238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 15, 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)

Splicing

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

Other links and lift over

dbSNP: rs3037626; hg19: chr20-42743205;