chr20-44113260-C-T

Position:

• chr20-44113260-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020433.5(JPH2):​c.*258G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 152,302 control chromosomes in the GnomAD database, including 811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (809 hom., cov: 32)
  • Exomes 𝑓: 0.098 (2 hom.)
• Consequence: JPH2 NM_020433.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.445

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 20-44113260-C-T is Benign according to our data. Variant chr20-44113260-C-T is described in ClinVar as [Benign]. Clinvar id is 1232267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JPH2	NM_020433.5	c.*258G>A		3_prime_UTR_variant	6/6	ENST00000372980.4	NP_065166.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JPH2	ENST00000372980.4	c.*258G>A		3_prime_UTR_variant	6/6	5	NM_020433.5	ENSP00000362071	P1

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 13989 AN: 151990 Hom.: 809 Cov.: 32

Gnomad AFR AF: 0.0274

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0581

Gnomad SAS AF: 0.0572

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.0891

GnomAD4 exome AF: 0.0979 AC: 19 AN: 194 Hom.: 2 Cov.: 0 AF XY: 0.0923 AC XY: 12 AN XY: 130

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0833

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0920 AC: 13989 AN: 152108 Hom.: 809 Cov.: 32 AF XY: 0.0909 AC XY: 6756 AN XY: 74346

Gnomad4 AFR AF: 0.0273

Gnomad4 AMR AF: 0.0788

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.0582

Gnomad4 SAS AF: 0.0578

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.0877

Alfa AF: 0.107 Hom.: 125

Bravo AF: 0.0859

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.37

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: rs13043824; hg19: chr20-42741900;