20-44114513-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020433.5(JPH2):c.*14+269C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,662 control chromosomes in the GnomAD database, including 13,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.41 (13467 hom., cov: 31)
• Consequence: JPH2 NM_020433.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 20-44114513-G-A is Benign according to our data. Variant chr20-44114513-G-A is described in ClinVar as [Benign]. Clinvar id is 1240694.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPH2	NM_020433.5	c.*14+269C>T		intron_variant		ENST00000372980.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPH2	ENST00000372980.4	c.*14+269C>T		intron_variant		5	NM_020433.5	P1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62250 AN: 151544 Hom.: 13455 Cov.: 31

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.411 AC: 62307 AN: 151662 Hom.: 13467 Cov.: 31 AF XY: 0.410 AC XY: 30378 AN XY: 74080

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.418

Alfa AF: 0.375 Hom.: 4259

Bravo AF: 0.420

Asia WGS AF: 0.490 AC: 1703 AN: 3478

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

Jun 19, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	13
Dann	Benign	0.61

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

LitVar

Other links and lift over

dbSNP: rs2867794; hg19: chr20-42743153;