20-44114565-AGT-A

Variant names:

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

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+216delAC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1180 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-AGT-A is Benign according to our data. Variant chr20-44114565-AGT-A is described in ClinVar as [Benign]. Clinvar id is 1294150.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 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+216delAC		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+215_*14+216delAC		intron_variant	Intron 5 of 5	5	NM_020433.5	ENSP00000362071.3

Frequencies

GnomAD3 genomes AF: 0.132 AC: 18623 AN: 141418 Hom.: 1178 Cov.: 0

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0809

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.132 AC: 18620 AN: 141514 Hom.: 1180 Cov.: 0 AF XY: 0.129 AC XY: 8814 AN XY: 68158

African (AFR) AF: 0.115 AC: 4390 AN: 38140

American (AMR) AF: 0.141 AC: 1989 AN: 14130

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 392 AN: 3340

East Asian (EAS) AF: 0.169 AC: 775 AN: 4596

South Asian (SAS) AF: 0.137 AC: 556 AN: 4064

European-Finnish (FIN) AF: 0.116 AC: 1050 AN: 9022

Middle Eastern (MID) AF: 0.199 AC: 53 AN: 266

European-Non Finnish (NFE) AF: 0.139 AC: 9083 AN: 65112

Other (OTH) AF: 0.133 AC: 261 AN: 1966

Alfa AF: 0.0874 Hom.: 238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.79
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: rs3037626; hg19: chr20-42743205;