chr14-75461528-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001135048.2(JDP2):​c.304C>T​(p.Arg102Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000269 in 1,599,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

JDP2
NM_001135048.2 missense, splice_region

Scores

2
6
11
Splicing: ADA: 0.4807
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.26300114).
BS2
High AC in GnomAdExome4 at 39 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
JDP2NM_001135048.2 linkuse as main transcriptc.304C>T p.Arg102Trp missense_variant, splice_region_variant 3/4 ENST00000651602.1 NP_001128520.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
JDP2ENST00000651602.1 linkuse as main transcriptc.304C>T p.Arg102Trp missense_variant, splice_region_variant 3/4 NM_001135048.2 ENSP00000498745 P1Q8WYK2-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152120
Hom.:
0
Cov.:
32
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:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000269
AC:
39
AN:
1447518
Hom.:
0
Cov.:
30
AF XY:
0.0000278
AC XY:
20
AN XY:
718476
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000476
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000193
Gnomad4 NFE exome
AF:
0.0000307
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152120
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000766
Hom.:
0
Bravo
AF:
0.0000227
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000828
AC:
1

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 submitterclinical testingAmbry GeneticsDec 22, 2023The c.337C>T (p.R113W) alteration is located in exon 3 (coding exon 3) of the JDP2 gene. This alteration results from a C to T substitution at nucleotide position 337, causing the arginine (R) at amino acid position 113 to be replaced by a tryptophan (W). 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
Uncertain
0.43
BayesDel_addAF
Benign
-0.022
T
BayesDel_noAF
Benign
-0.27
CADD
Pathogenic
34
DANN
Uncertain
1.0
DEOGEN2
Benign
0.38
T;T;T;T;.
Eigen
Benign
0.11
Eigen_PC
Benign
0.085
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Pathogenic
0.98
.;D;D;.;D
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.26
T;T;T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
1.6
L;.;L;L;.
MutationTaster
Benign
0.92
D;D;D;D
PrimateAI
Pathogenic
0.79
T
PROVEAN
Uncertain
-4.1
D;D;D;D;D
REVEL
Benign
0.22
Sift
Uncertain
0.0010
D;D;D;D;D
Sift4G
Uncertain
0.0050
D;D;D;D;D
Polyphen
0.99
D;.;D;D;.
Vest4
0.43
MVP
0.13
MPC
1.1
ClinPred
0.84
D
GERP RS
1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.66
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.48
dbscSNV1_RF
Benign
0.39
SpliceAI score (max)
0.10
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.

Other links and lift over

dbSNP: rs371436905; hg19: chr14-75928231; COSMIC: COSV50867839; API