NM_020433.5:c.1289-7C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020433.5(JPH2):c.1289-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,546,950 control chromosomes in the GnomAD database, including 631 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 42 hom., cov: 32)

Exomes 𝑓: 0.026 ( 589 hom. )

Consequence

JPH2
NM_020433.5 splice_region, intron

Scores

Splicing: ADA: 0.00007215

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.0320

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: 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

JPH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 20-44116393-G-A is Benign according to our data. Variant chr20-44116393-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0205 (3120/152314) while in subpopulation NFE AF = 0.0306 (2083/68012). AF 95% confidence interval is 0.0295. There are 42 homozygotes in GnomAd4. There are 1523 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 42 SD,AD,Unknown,AR 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.1289-7C>T		splice_region 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.1289-7C>T	splice_region intron	N/A	ENSP00000362071.3	Q9BR39-1
JPH2	ENST00000900331.1		c.1370-7C>T	splice_region intron	N/A	ENSP00000570390.1
JPH2	ENST00000950207.1		c.1352-7C>T	splice_region intron	N/A	ENSP00000620266.1

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3119

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00524

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0226

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.0311

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0306

Gnomad OTH

AF:

0.0229

GnomAD2 exomes

AF:

0.0189

AC:

2616

AN:

138096

AF XY:

0.0190

show subpopulations

Gnomad AFR exome

AF:

0.00430

Gnomad AMR exome

AF:

0.0155

Gnomad ASJ exome

AF:

0.0169

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0260

Gnomad NFE exome

AF:

0.0306

Gnomad OTH exome

AF:

0.0207

GnomAD4 exome

AF:

0.0265

AC:

36894

AN:

1394636

Hom.:

589

Cov.:

AF XY:

0.0261

AC XY:

17943

AN XY:

687918

show subpopulations

African (AFR)

AF:

0.00403

AC:

127

AN:

31522

American (AMR)

AF:

0.0157

AC:

560

AN:

35646

Ashkenazi Jewish (ASJ)

AF:

0.0155

AC:

390

AN:

25146

East Asian (EAS)

AF:

0.00

AC:

AN:

35698

South Asian (SAS)

AF:

0.00636

AC:

503

AN:

79104

European-Finnish (FIN)

AF:

0.0265

AC:

1209

AN:

45598

Middle Eastern (MID)

AF:

0.0236

AC:

130

AN:

5518

European-Non Finnish (NFE)

AF:

0.0304

AC:

32790

AN:

1078514

Other (OTH)

AF:

0.0205

AC:

1185

AN:

57890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

2006

4012

6018

8024

10030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1200

2400

3600

4800

6000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0205

AC:

3120

AN:

152314

Hom.:

Cov.:

AF XY:

0.0204

AC XY:

1523

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00522

AC:

217

AN:

41568

American (AMR)

AF:

0.0226

AC:

346

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00683

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0311

AC:

330

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0306

AC:

2083

AN:

68012

Other (OTH)

AF:

0.0227

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

162

324

487

649

811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0284

Hom.:

Bravo

AF:

0.0191

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (3)

Hypertrophic cardiomyopathy 17 (2)

Hypertrophic cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.6

(source)

DANN

Benign

0.65

PhyloP100

0.032

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000072

dbscSNV1_RF

Benign

0.0

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over