Variant 6-15468547-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_004973.4(JARID2):c.499C>T(p.Pro167Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,612,492 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

JARID2
NM_004973.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.91

Variant links:

Genes affected

JARID2 (HGNC:6196): (jumonji and AT-rich interaction domain containing 2) This gene encodes a Jumonji- and AT-rich interaction domain (ARID)-domain-containing protein. The encoded protein is a DNA-binding protein that functions as a transcriptional repressor. This protein interacts with the Polycomb repressive complex 2 (PRC2) which plays an essential role in regulating gene expression during embryonic development. This protein facilitates the recruitment of the PRC2 complex to target genes. Alternate splicing results in multiple transcript variants. Mutations in this gene are associated with chronic myeloid malignancies. [provided by RefSeq, May 2012]

JARID2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), JARID2. . Gene score misZ 2.6866 (greater than the threshold 3.09). Trascript score misZ 3.2473 (greater than threshold 3.09). GenCC has associacion of gene with syndromic intellectual disability, developmental delay with variable intellectual disability and dysmorphic facies.

BP4

Computational evidence support a benign effect (MetaRNN=0.20698455).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JARID2	NM_004973.4 linkuse as main transcript	c.499C>T	p.Pro167Ser	missense_variant	5/18	ENST00000341776.7	NP_004964.2	Q92833-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JARID2	ENST00000341776.7 linkuse as main transcript	c.499C>T	p.Pro167Ser	missense_variant	5/18	1	NM_004973.4	ENSP00000341280.2		Q92833-1
JARID2	ENST00000397311 linkuse as main transcript	c.-18C>T		5_prime_UTR_variant	5/18	2		ENSP00000380478.3		Q92833-3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00000400

AC:

AN:

250242

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135290

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:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460420

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726480

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.00

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.499C>T (p.P167S) alteration is located in exon 5 (coding exon 5) of the JARID2 gene. This alteration results from a C to T substitution at nucleotide position 499, causing the proline (P) at amino acid position 167 to be replaced by a serine (S). 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

0.11

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Benign

-0.039

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0061

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.3

REVEL

Benign

0.057

Sift

Benign

0.31

Sift4G

Benign

0.46

Polyphen

0.46

Vest4

0.32

MutPred

0.50

Gain of phosphorylation at P167 (P = 0.0377);

MVP

0.27

MPC

0.18

ClinPred

0.35

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.28

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