Genetic Variant JDP2:p.Arg96His (chr14-75461511-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001135048.2(JDP2):c.287G>A(p.Arg96His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000286 in 1,606,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

JDP2
NM_001135048.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90

Variant links:

Genes affected

JDP2 (HGNC:17546): (Jun dimerization protein 2) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

JDP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JDP2	NM_001135048.2 link	c.287G>A	p.Arg96His	missense_variant	Exon 3 of 4	ENST00000651602.1	NP_001128520.1	Q8WYK2-1A0A024R6D7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JDP2	ENST00000651602.1 link	c.287G>A	p.Arg96His	missense_variant	Exon 3 of 4		NM_001135048.2	ENSP00000498745.1		Q8WYK2-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152156

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000169

AC:

AN:

236540

Hom.:

AF XY:

0.0000236

AC XY:

AN XY:

127002

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000372

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000302

AC:

AN:

1454656

Hom.:

Cov.:

AF XY:

0.0000346

AC XY:

AN XY:

722626

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.320G>A (p.R107H) alteration is located in exon 3 (coding exon 3) of the JDP2 gene. This alteration results from a G to A substitution at nucleotide position 320, causing the arginine (R) at amino acid position 107 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.29

T;T;T;T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

.;D;D;.;D

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.52

D;D;D;D;D

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.0

L;.;L;L;.

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.2

D;D;D;D;D

REVEL

Uncertain

0.35

Sift

Benign

0.14

T;T;T;T;D

Sift4G

Uncertain

0.018

D;D;D;D;D

Polyphen

1.0

D;.;D;D;.

Vest4

0.68

MutPred

0.39

Loss of MoRF binding (P = 0.0569);Loss of MoRF binding (P = 0.0569);Loss of MoRF binding (P = 0.0569);Loss of MoRF binding (P = 0.0569);.;

MVP

0.40

MPC

1.4

ClinPred

0.94

GERP RS

4.8

Varity_R

0.15

gMVP

0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over