Variant 5-134566249-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001388185.1(JADE2):c.1103G>T(p.Gly368Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,614,122 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 20 hom., cov: 31)

Exomes 𝑓: 0.014 ( 172 hom. )

Consequence

JADE2
NM_001388185.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.98

Variant links:

Genes affected

JADE2 (HGNC:22984): (jade family PHD finger 2) Predicted to enable ubiquitin protein ligase activity. Involved in histone acetylation. Located in nucleoplasm. Part of histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

JADE2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002391994).

BP6

Variant 5-134566249-G-T is Benign according to our data. Variant chr5-134566249-G-T is described in ClinVar as [Benign]. Clinvar id is 3390326.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0126 (1920/152252) while in subpopulation NFE AF= 0.0168 (1145/68024). AF 95% confidence interval is 0.016. There are 20 homozygotes in gnomad4. There are 987 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE2	NM_001388185.1 link	c.1103G>T	p.Gly368Val	missense_variant	9/12	ENST00000681547.2	NP_001375114.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JADE2	ENST00000681547.2 link	c.1103G>T	p.Gly368Val	missense_variant	9/12		NM_001388185.1	ENSP00000505514.1		G3XAA4

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1920

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00799

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.0425

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0168

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.0133

AC:

3353

AN:

251472

Hom.:

AF XY:

0.0133

AC XY:

1808

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00463

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00529

Gnomad FIN exome

AF:

0.0423

Gnomad NFE exome

AF:

0.0164

Gnomad OTH exome

AF:

0.0140

GnomAD4 exome

AF:

0.0140

AC:

20395

AN:

1461870

Hom.:

172

Cov.:

AF XY:

0.0140

AC XY:

10160

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00215

Gnomad4 AMR exome

AF:

0.00487

Gnomad4 ASJ exome

AF:

0.0138

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00568

Gnomad4 FIN exome

AF:

0.0419

Gnomad4 NFE exome

AF:

0.0146

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.0126

AC:

1920

AN:

152252

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

987

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.00798

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.0425

Gnomad4 NFE

AF:

0.0168

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.0151

Hom.:

Bravo

AF:

0.00932

TwinsUK

AF:

0.0143

AC:

ALSPAC

AF:

0.0132

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0141

AC:

121

ExAC

AF:

0.0131

AC:

1592

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0152

EpiControl

AF:

0.0117

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

JADE2: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

T;T;T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.035

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.74

T;T;T;T

MetaRNN

Benign

0.0024

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;.;.;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.056

Sift

Uncertain

0.010

D;D;D;D

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.0080, 0.035

.;.;B;B

Vest4

0.20

MPC

1.1

ClinPred

0.0081

GERP RS

3.7

Varity_R

0.10

gMVP

0.51

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