6-15513251-G-A

Variant names:

• chr6-15513251-G-A
• rs2235258
• NM_004973.4:c.3279G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004973.4(JARID2):​c.3279G>A​(p.Leu1093Leu) 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
• Publications: 20 publications found

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 Gene-Disease associations (from GenCC):

• developmental delay with variable intellectual disability and dysmorphic facies

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004973.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JARID2	NM_004973.4	MANE Select	c.3279G>A	p.Leu1093Leu	synonymous	Exon 16 of 18	NP_004964.2
	JARID2	NM_001267040.1		c.2763G>A	p.Leu921Leu	synonymous	Exon 16 of 18	NP_001253969.1	Q92833-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JARID2	ENST00000341776.7	TSL:1 MANE Select	c.3279G>A	p.Leu1093Leu	synonymous	Exon 16 of 18	ENSP00000341280.2	Q92833-1
	JARID2	ENST00000853926.1		c.3279G>A	p.Leu1093Leu	synonymous	Exon 17 of 19	ENSP00000523985.1
	JARID2	ENST00000853927.1		c.3279G>A	p.Leu1093Leu	synonymous	Exon 17 of 19	ENSP00000523986.1

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

GnomAD2 exomes AF: 0.722 AC: 139195 AN: 192860 AF XY: 0.728

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 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

African (AFR) AF: 0.358 AC: 11756 AN: 32812

American (AMR) AF: 0.661 AC: 24414 AN: 36918

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 20881 AN: 24998

East Asian (EAS) AF: 0.691 AC: 26275 AN: 38048

South Asian (SAS) AF: 0.700 AC: 57524 AN: 82212

European-Finnish (FIN) AF: 0.822 AC: 41474 AN: 50466

Middle Eastern (MID) AF: 0.717 AC: 3804 AN: 5306

European-Non Finnish (NFE) AF: 0.765 AC: 831565 AN: 1087424

Other (OTH) AF: 0.733 AC: 42920 AN: 58580

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

African (AFR) AF: 0.373 AC: 15477 AN: 41522

American (AMR) AF: 0.669 AC: 10240 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2912 AN: 3472

East Asian (EAS) AF: 0.664 AC: 3421 AN: 5150

South Asian (SAS) AF: 0.697 AC: 3361 AN: 4824

European-Finnish (FIN) AF: 0.817 AC: 8652 AN: 10592

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 52000 AN: 67984

Other (OTH) AF: 0.658 AC: 1388 AN: 2110

Alfa AF: 0.727 Hom.: 149079

Bravo AF: 0.623

Asia WGS AF: 0.648 AC: 2255 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	10
DANN	Benign	0.82
PhyloP100		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2235258; hg19: chr6-15513482; COSMIC: COSV59185201; COSMIC: COSV59185201;