Variant 14-75438110-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001135048.2(JDP2):c.190G>C(p.Val64Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

JDP2
NM_001135048.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.54

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:

JDP2 (HGNC:):

JDP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16504198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JDP2	NM_001135048.2 linkuse as main transcript	c.190G>C	p.Val64Leu	missense_variant	2/4	ENST00000651602.1	NP_001128520.1	Q8WYK2-1A0A024R6D7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JDP2	ENST00000651602.1 linkuse as main transcript	c.190G>C	p.Val64Leu	missense_variant	2/4		NM_001135048.2	ENSP00000498745.1		Q8WYK2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455410

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723072

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:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.223G>C (p.V75L) alteration is located in exon 2 (coding exon 2) of the JDP2 gene. This alteration results from a G to C substitution at nucleotide position 223, causing the valine (V) at amino acid position 75 to be replaced by a leucine (L). 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

Benign

0.098

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;T;T;T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.066

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

.;D;D;.;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.17

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

M;.;M;M;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.72

N;N;N;N;N

REVEL

Benign

0.064

Sift

Benign

0.23

T;T;T;T;T

Sift4G

Benign

0.57

T;T;T;T;T

Polyphen

0.45

B;.;B;B;.

Vest4

0.21

MutPred

0.24

Loss of methylation at K65 (P = 0.0588);Loss of methylation at K65 (P = 0.0588);Loss of methylation at K65 (P = 0.0588);Loss of methylation at K65 (P = 0.0588);.;

MVP

0.043

MPC

0.58

ClinPred

0.88

GERP RS

3.3

Varity_R

0.12

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over