rs2235258

Positions:

• chr6-15513251-G-A
• chr6-15513251-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004973.4(JARID2):​c.3279G>A​(p.Leu1093=) variant causes a synonymous change. The variant allele was found at a frequency of 0.739 in 1,568,922 control chromosomes in the GnomAD database, including 434,832 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (34247 hom., cov: 34)
  • Exomes 𝑓: 0.75 (400585 hom.)
• Consequence: JARID2 NM_004973.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.52

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JARID2	NM_004973.4	c.3279G>A	p.Leu1093=	synonymous_variant	16/18	ENST00000341776.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JARID2	ENST00000341776.7	c.3279G>A	p.Leu1093=	synonymous_variant	16/18	1	NM_004973.4	P2
JARID2	ENST00000397311.4	c.2763G>A	p.Leu921=	synonymous_variant	16/18	2		A2

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98424 AN: 152040 Hom.: 34238 Cov.: 34

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.660

GnomAD3 exomes AF: 0.722 AC: 139195 AN: 192860 Hom.: 51386 AF XY: 0.728 AC XY: 75385 AN XY: 103506

Gnomad AFR exome AF: 0.364

Gnomad AMR exome AF: 0.659

Gnomad ASJ exome AF: 0.835

Gnomad EAS exome AF: 0.673

Gnomad SAS exome AF: 0.699

Gnomad FIN exome AF: 0.827

Gnomad NFE exome AF: 0.772

Gnomad OTH exome AF: 0.742

GnomAD4 exome AF: 0.749 AC: 1060613 AN: 1416764 Hom.: 400585 Cov.: 54 AF XY: 0.749 AC XY: 523986 AN XY: 699684

Gnomad4 AFR exome AF: 0.358

Gnomad4 AMR exome AF: 0.661

Gnomad4 ASJ exome AF: 0.835

Gnomad4 EAS exome AF: 0.691

Gnomad4 SAS exome AF: 0.700

Gnomad4 FIN exome AF: 0.822

Gnomad4 NFE exome AF: 0.765

Gnomad4 OTH exome AF: 0.733

GnomAD4 genome AF: 0.647 AC: 98457 AN: 152158 Hom.: 34247 Cov.: 34 AF XY: 0.652 AC XY: 48489 AN XY: 74402

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.658

Alfa AF: 0.742 Hom.: 60961

Bravo AF: 0.623

Asia WGS AF: 0.648 AC: 2255 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	10
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2235258; hg19: chr6-15513482; COSMIC: COSV59185201; COSMIC: COSV59185201;