20-44114609-T-C

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+173A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 143,944 control chromosomes in the GnomAD database, including 7,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (7647 hom., cov: 27)
• Consequence: JPH2 NM_020433.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.507

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=-0.87).
• BP6: Variant 20-44114609-T-C is Benign according to our data. Variant chr20-44114609-T-C is described in ClinVar as [Benign]. Clinvar id is 1231105.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JPH2	NM_020433.5	c.*14+173A>G		intron_variant		ENST00000372980.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JPH2	ENST00000372980.4	c.*14+173A>G		intron_variant		5	NM_020433.5	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 46803 AN: 143842 Hom.: 7640 Cov.: 27

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.325 AC: 46843 AN: 143944 Hom.: 7647 Cov.: 27 AF XY: 0.321 AC XY: 22438 AN XY: 69882

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.313

Alfa AF: 0.271 Hom.: 1198

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 08, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.1
Dann	Benign	0.75

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: rs56170305; hg19: chr20-42743249; COSMIC: COSV65905929;