NM_020433.5:c.*14+209_*14+216delACACACAC

Variant names:

• chr20-44114565-AGTGTGTGT-A
• rs3037626
• NM_020433.5:c.*14+209_*14+216delACACACAC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020433.5(JPH2):​c.*14+209_*14+216delACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4010 hom., cov: 0)
• Consequence: JPH2 NM_020433.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.794
• Publications: 0 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: AR, SD, 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 -10 ACMG points.

• BP6: Variant 20-44114565-AGTGTGTGT-A is Benign according to our data. Variant chr20-44114565-AGTGTGTGT-A is described in ClinVar as Benign. ClinVar VariationId is 1265714.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 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+209_*14+216delACACACAC		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+209_*14+216delACACACAC		intron	N/A	ENSP00000362071.3	Q9BR39-1
	JPH2	ENST00000900330.1		c.*223_*230delACACACAC		3_prime_UTR	Exon 5 of 5	ENSP00000570389.1
	JPH2	ENST00000900331.1		c.*14+209_*14+216delACACACAC		intron	N/A	ENSP00000570390.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 32617 AN: 141676 Hom.: 4010 Cov.: 0

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.230 AC: 32635 AN: 141774 Hom.: 4010 Cov.: 0 AF XY: 0.230 AC XY: 15676 AN XY: 68276

African (AFR) AF: 0.134 AC: 5125 AN: 38248

American (AMR) AF: 0.210 AC: 2965 AN: 14146

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1062 AN: 3348

East Asian (EAS) AF: 0.0677 AC: 312 AN: 4608

South Asian (SAS) AF: 0.216 AC: 879 AN: 4066

European-Finnish (FIN) AF: 0.305 AC: 2754 AN: 9026

Middle Eastern (MID) AF: 0.200 AC: 54 AN: 270

European-Non Finnish (NFE) AF: 0.289 AC: 18840 AN: 65216

Other (OTH) AF: 0.225 AC: 442 AN: 1968

Alfa AF: 0.277 Hom.: 238

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3037626;

hg19: chr20-42743205;

COSMIC: COSV65902460;