rs1012335909

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020433.5(JPH2):c.439G>T(p.Val147Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,592,752 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V147M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

JPH2
NM_020433.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

Publications

2 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, 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

JPH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH2	NM_020433.5	MANE Select	c.439G>T	p.Val147Leu	missense	Exon 2 of 6	NP_065166.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JPH2	ENST00000372980.4	TSL:5 MANE Select	c.439G>T	p.Val147Leu	missense	Exon 2 of 6	ENSP00000362071.3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

210400

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1440546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714772

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33050

American (AMR)

AF:

0.00

AC:

AN:

42600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25736

East Asian (EAS)

AF:

0.00

AC:

AN:

38646

South Asian (SAS)

AF:

0.00

AC:

AN:

82966

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50192

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5522

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1102308

Other (OTH)

AF:

0.00

AC:

AN:

59526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.4

PhyloP100

7.5

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.37

Sift

Uncertain

0.0050

Sift4G

Benign

0.080

Polyphen

0.96

Vest4

0.66

MutPred

0.54

Loss of sheet (P = 0.0817)

MVP

0.87

ClinPred

0.99

GERP RS

3.3

Varity_R

0.55

gMVP

0.47

Mutation Taster

=60/40

polymorphism

(source)

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

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

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over