20-44114565-AGTGTGTGT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020433.5(JPH2):c.*14+209_*14+216del 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.794

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
JPH2	NM_020433.5	c.*14+209_*14+216del		intron_variant		ENST00000372980.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPH2	ENST00000372980.4	c.*14+209_*14+216del		intron_variant		5	NM_020433.5	P1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 32617 AN: 141676 Hom.: 4010 Cov.: 0

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.: 0 AF XY: 0.230 AC XY: 15676 AN XY: 68276

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.0677

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.225

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3037626; hg19: chr20-42743205;