rs2072822

Variant names:

• chr6-15517428-C-A
• rs2072822
• NM_004973.4:c.3558+160C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-15517428-C-A
• chr6-15517428-C-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+160C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,142 control chromosomes in the GnomAD database, including 4,732 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 0.23 (4732 hom., cov: 33)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.3558+160C>A		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+160C>A		intron_variant	Intron 17 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.3042+160C>A		intron_variant	Intron 17 of 17	2		ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34752 AN: 152024 Hom.: 4734 Cov.: 33

Gnomad AFR AF: 0.0846

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.228 AC: 34753 AN: 152142 Hom.: 4732 Cov.: 33 AF XY: 0.237 AC XY: 17613 AN XY: 74370

African (AFR) AF: 0.0845 AC: 3511 AN: 41552

American (AMR) AF: 0.282 AC: 4319 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 981 AN: 3472

East Asian (EAS) AF: 0.424 AC: 2174 AN: 5130

South Asian (SAS) AF: 0.347 AC: 1674 AN: 4822

European-Finnish (FIN) AF: 0.342 AC: 3618 AN: 10586

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.260 AC: 17679 AN: 67974

Other (OTH) AF: 0.219 AC: 463 AN: 2112

Alfa AF: 0.233 Hom.: 4302

Bravo AF: 0.217

Asia WGS AF: 0.365 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.77
PhyloP100		0.048
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: rs2072822; hg19: chr6-15517659;