6-15468645-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_004973.4(JARID2):c.597C>G(p.Thr199=) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T199T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.092 (892 hom., cov: 30)
  • Exomes 𝑓: 0.12 (11820 hom.)
• Consequence: JARID2 NM_004973.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.90

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]

ACMG classification

Verdict is Benign. Variant got -19 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_multiple_submitters_no_conflicts, 2 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/exons	MANE	UniProt
JARID2	NM_004973.4	c.597C>G	p.Thr199=	synonymous_variant	5/18	ENST00000341776.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JARID2	ENST00000341776.7	c.597C>G	p.Thr199=	synonymous_variant	5/18	1	NM_004973.4	P2
JARID2	ENST00000397311.4	c.81C>G	p.Thr27=	synonymous_variant	5/18	2		A2

Frequencies

GnomAD3 genomes AF: 0.0922 AC: 14009 AN: 152012 Hom.: 891 Cov.: 30

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

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.: 32 AF XY: 0.121 AC XY: 87987 AN XY: 726948

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.: 30 AF XY: 0.0895 AC XY: 6659 AN XY: 74368

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, multiple submitters, no conflicts

Submissions by phenotype

JARID2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 01, 2019

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	12
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

Other links and lift over

dbSNP: rs7768621; hg19: chr6-15468876; COSMIC: COSV59185185;