NM_020433.5:c.*14+199_*14+216delACACACACACACACACAC

Variant names:

• chr20-44114565-AGTGTGTGTGTGTGTGTGT-A
• rs3037626
• NM_020433.5:c.*14+199_*14+216delACACACACACACACACAC

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+199_*14+216delACACACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1036 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, 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 -10 ACMG points.

• BP6: Variant 20-44114565-AGTGTGTGTGTGTGTGTGT-A is Benign according to our data. Variant chr20-44114565-AGTGTGTGTGTGTGTGTGT-A is described in ClinVar as [Benign]. Clinvar id is 1233197.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JPH2	NM_020433.5	c.*14+199_*14+216delACACACACACACACACAC		intron_variant	Intron 5 of 5	ENST00000372980.4	NP_065166.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JPH2	ENST00000372980.4	c.*14+199_*14+216delACACACACACACACACAC		intron_variant	Intron 5 of 5	5	NM_020433.5	ENSP00000362071.3

Frequencies

GnomAD3 genomes AF: 0.108 AC: 15323 AN: 141888 Hom.: 1036 Cov.: 0

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0882

Gnomad AMR AF: 0.0748

Gnomad ASJ AF: 0.0624

Gnomad EAS AF: 0.0268

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0654

Gnomad MID AF: 0.0582

Gnomad NFE AF: 0.0768

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.108 AC: 15349 AN: 141986 Hom.: 1036 Cov.: 0 AF XY: 0.106 AC XY: 7243 AN XY: 68382

African (AFR) AF: 0.207 AC: 7913 AN: 38308

American (AMR) AF: 0.0747 AC: 1058 AN: 14162

Ashkenazi Jewish (ASJ) AF: 0.0624 AC: 209 AN: 3348

East Asian (EAS) AF: 0.0267 AC: 123 AN: 4608

South Asian (SAS) AF: 0.0294 AC: 120 AN: 4076

European-Finnish (FIN) AF: 0.0654 AC: 592 AN: 9058

Middle Eastern (MID) AF: 0.0630 AC: 17 AN: 270

European-Non Finnish (NFE) AF: 0.0768 AC: 5014 AN: 65304

Other (OTH) AF: 0.114 AC: 225 AN: 1968

Alfa AF: 0.0585 Hom.: 238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 10, 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
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3037626; hg19: chr20-42743205;