20-44114609-T-C

Variant names:

• chr20-44114609-T-C
• rs56170305
• NM_020433.5:c.*14+173A>G

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.*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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.507
• 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 Submitted by: Labcorp Genetics (formerly Invitae)
• dilated cardiomyopathy

  Inheritance: SD, AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: ClinGen
• 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

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1231105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020433.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH2	NM_020433.5	MANE Select	c.*14+173A>G		intron	N/A	NP_065166.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH2	ENST00000372980.4	TSL:5 MANE Select	c.*14+173A>G		intron	N/A	ENSP00000362071.3	Q9BR39-1
	JPH2	ENST00000900330.1		c.*187A>G		3_prime_UTR	Exon 5 of 5	ENSP00000570389.1
	JPH2	ENST00000900331.1		c.*14+173A>G		intron	N/A	ENSP00000570390.1

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

African (AFR) AF: 0.412 AC: 15984 AN: 38752

American (AMR) AF: 0.240 AC: 3441 AN: 14330

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1215 AN: 3362

East Asian (EAS) AF: 0.120 AC: 548 AN: 4576

South Asian (SAS) AF: 0.225 AC: 982 AN: 4358

European-Finnish (FIN) AF: 0.314 AC: 3056 AN: 9722

Middle Eastern (MID) AF: 0.197 AC: 54 AN: 274

European-Non Finnish (NFE) AF: 0.314 AC: 20629 AN: 65676

Other (OTH) AF: 0.313 AC: 631 AN: 2014

Alfa AF: 0.292 Hom.: 2487

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.75
PhyloP100		-0.51
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: rs56170305; hg19: chr20-42743249; COSMIC: COSV65905929;