Variant NM_004973.4:c.597C>G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_004973.4(JARID2):c.597C>G(p.Thr199Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,613,434 control chromosomes in the GnomAD database, including 12,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.092 ( 892 hom., cov: 30)

Exomes 𝑓: 0.12 ( 11820 hom. )

Consequence

JARID2
NM_004973.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.90

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 6-15468645-C-G is Benign according to our data. Variant chr6-15468645-C-G is described in ClinVar as [Benign]. Clinvar id is 1302851.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.9 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4 link	c.597C>G	p.Thr199Thr	synonymous_variant	Exon 5 of 18	ENST00000341776.7	NP_004964.2	Q92833-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JARID2	ENST00000341776.7 link	c.597C>G	p.Thr199Thr	synonymous_variant	Exon 5 of 18	1	NM_004973.4	ENSP00000341280.2		Q92833-1
JARID2	ENST00000397311.4 link	c.81C>G	p.Thr27Thr	synonymous_variant	Exon 5 of 18	2		ENSP00000380478.3		Q92833-3

Frequencies

GnomAD3 genomes

AF:

0.0922

AC:

14009

AN:

152012

Hom.:

891

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0235

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.0844

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.000965

Gnomad SAS

AF:

0.0792

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.100

GnomAD3 exomes

AF:

0.100

AC:

25191

AN:

251236

Hom.:

1567

AF XY:

0.104

AC XY:

14059

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.0206

Gnomad AMR exome

AF:

0.0547

Gnomad ASJ exome

AF:

0.176

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.0828

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.122

AC:

178857

AN:

1461304

Hom.:

11820

Cov.:

AF XY:

0.121

AC XY:

87987

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.0174

Gnomad4 AMR exome

AF:

0.0579

Gnomad4 ASJ exome

AF:

0.177

Gnomad4 EAS exome

AF:

0.000579

Gnomad4 SAS exome

AF:

0.0854

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.0921

AC:

14005

AN:

152130

Hom.:

892

Cov.:

AF XY:

0.0895

AC XY:

6659

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0234

Gnomad4 AMR

AF:

0.0842

Gnomad4 ASJ

AF:

0.173

Gnomad4 EAS

AF:

0.000967

Gnomad4 SAS

AF:

0.0795

Gnomad4 FIN

AF:

0.117

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.0985

Alfa

AF:

0.0823

Hom.:

158

Bravo

AF:

0.0890

EpiCase

AF:

0.130

EpiControl

AF:

0.133

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

JARID2-related disorder

Benign:1

Nov 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Jul 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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