Genetic Variant NM_001135048.2:c.13C>A (chr14-75437933-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001135048.2(JDP2):c.13C>A(p.Gln5Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

JDP2
NM_001135048.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.11

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35800627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JDP2	NM_001135048.2 link	c.13C>A	p.Gln5Lys	missense_variant	Exon 2 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.13C>A	p.Gln5Lys	missense_variant	Exon 2 of 4		NM_001135048.2	ENSP00000498745.1		Q8WYK2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.86e-7

AC:

AN:

1457670

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724684

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.46C>A (p.Q16K) alteration is located in exon 2 (coding exon 2) of the JDP2 gene. This alteration results from a C to A substitution at nucleotide position 46, causing the glutamine (Q) at amino acid position 16 to be replaced by a lysine (K). 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

0.13

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

T;T;T;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.052

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

.;T;T;.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.36

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;L;L;.

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.9

N;N;N;N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0020

D;D;D;D;T

Sift4G

Benign

0.34

T;T;T;T;T

Polyphen

0.0020

B;.;B;B;.

Vest4

0.73

MutPred

0.29

Gain of catalytic residue at I6 (P = 0);Gain of catalytic residue at I6 (P = 0);Gain of catalytic residue at I6 (P = 0);Gain of catalytic residue at I6 (P = 0);.;

MVP

0.78

MPC

0.59

ClinPred

0.91

GERP RS

4.7

Varity_R

0.52

gMVP

0.68

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