Genetic Variant JPH2:c.*14+201_*14+216delACACACACACACACAC (chr20-44114565-AGTGTGTGTGTGTGTGT-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_020433.5(JPH2):c.*14+201_*14+216delACACACACACACACAC 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 0)

Consequence

JPH2
NM_020433.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.794

Publications

0 publications found

Variant links:

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

JPH2 links:

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new If you want to explore the variant's impact on the transcript NM_020433.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 Unknown,SD,AR,AD gene

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+201_14+216delACACACACACACACAC		intron	N/A	NP_065166.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
JPH2	ENST00000372980.4	TSL:5 MANE Select	c.14+201_14+216delACACACACACACACAC	intron	N/A	ENSP00000362071.3	Q9BR39-1
JPH2	ENST00000900330.1		c.215_230delACACACACACACACAC	3_prime_UTR	Exon 5 of 5	ENSP00000570389.1
JPH2	ENST00000900331.1		c.14+201_14+216delACACACACACACACAC	intron	N/A	ENSP00000570390.1

Frequencies

GnomAD3 genomes

AF:

0.00352

AC:

499

AN:

141904

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00785

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00106

Gnomad ASJ

AF:

0.0305

Gnomad EAS

AF:

0.000649

Gnomad SAS

AF:

0.00147

Gnomad FIN

AF:

0.00298

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000689

Gnomad OTH

AF:

0.000513

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

GnomAD4 genome

AF:

0.00353

AC:

501

AN:

142002

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

249

AN XY:

68390

show subpopulations

African (AFR)

AF:

0.00788

AC:

302

AN:

38316

American (AMR)

AF:

0.00106

AC:

AN:

14168

Ashkenazi Jewish (ASJ)

AF:

0.0305

AC:

102

AN:

3348

East Asian (EAS)

AF:

0.000651

AC:

AN:

4608

South Asian (SAS)

AF:

0.00147

AC:

AN:

4076

European-Finnish (FIN)

AF:

0.00298

AC:

AN:

9054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.000689

AC:

AN:

65310

Other (OTH)

AF:

0.000508

AC:

AN:

1970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.79

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.

Publications

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20-44114565-AGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over