rs2072821

Variant names:

• chr6-15517805-G-C
• rs2072821
• NM_004973.4:c.3558+537G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-15517805-G-C
• chr6-15517805-G-T

Variant summary

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

The NM_004973.4(JARID2):​c.3558+537G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,176 control chromosomes in the GnomAD database, including 4,998 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 0.24 (4998 hom., cov: 33)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.787
• Publications: 0 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: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.3558+537G>C		intron_variant	Intron 17 of 17	ENST00000341776.7	NP_004964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JARID2	ENST00000341776.7	c.3558+537G>C		intron_variant	Intron 17 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.3042+537G>C		intron_variant	Intron 17 of 17	2		ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35958 AN: 152058 Hom.: 5000 Cov.: 33

Gnomad AFR AF: 0.0938

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.229

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.236 AC: 35961 AN: 152176 Hom.: 4998 Cov.: 33 AF XY: 0.245 AC XY: 18236 AN XY: 74404

African (AFR) AF: 0.0938 AC: 3896 AN: 41554

American (AMR) AF: 0.287 AC: 4397 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 984 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2229 AN: 5150

South Asian (SAS) AF: 0.352 AC: 1697 AN: 4820

European-Finnish (FIN) AF: 0.348 AC: 3683 AN: 10580

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18264 AN: 67982

Other (OTH) AF: 0.229 AC: 484 AN: 2116

Alfa AF: 0.252 Hom.: 646

Bravo AF: 0.224

Asia WGS AF: 0.376 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.72
DANN	Benign	0.74
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2072821; hg19: chr6-15518036;