20-44113260-C-T

Variant names:

• chr20-44113260-C-T
• rs13043824
• NM_020433.5:c.*258G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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 rank	MANE	Protein	UniProt
JPH2	NM_020433.5	c.*258G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000372980.4	NP_065166.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JPH2	ENST00000372980.4	c.*258G>A		3_prime_UTR_variant	Exon 6 of 6	5	NM_020433.5	ENSP00000362071.3

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

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.0833 AC: 2 AN: 24

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.118 AC: 16 AN: 136

Other (OTH) AF: 0.100 AC: 1 AN: 10

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

African (AFR) AF: 0.0273 AC: 1134 AN: 41508

American (AMR) AF: 0.0788 AC: 1206 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3468

East Asian (EAS) AF: 0.0582 AC: 301 AN: 5170

South Asian (SAS) AF: 0.0578 AC: 279 AN: 4824

European-Finnish (FIN) AF: 0.140 AC: 1481 AN: 10582

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8596 AN: 67942

Other (OTH) AF: 0.0877 AC: 185 AN: 2110

Alfa AF: 0.109 Hom.: 286

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.37
PhyloP100		-0.45
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: rs13043824; hg19: chr20-42741900;