6-15516478-T-C

Variant names:

• chr6-15516478-T-C
• rs1474587
• NM_004973.4:c.3451-683T>C

Variant summary

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

The NM_004973.4(JARID2):​c.3451-683T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,226 control chromosomes in the GnomAD database, including 51,841 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 0.82 (51841 hom., cov: 33)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 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.3451-683T>C		intron	N/A	NP_004964.2
	JARID2	NM_001267040.1		c.2935-683T>C		intron	N/A	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.3451-683T>C		intron	N/A	ENSP00000341280.2	Q92833-1
	JARID2	ENST00000853926.1		c.3451-683T>C		intron	N/A	ENSP00000523985.1
	JARID2	ENST00000853927.1		c.3451-683T>C		intron	N/A	ENSP00000523986.1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125316 AN: 152108 Hom.: 51808 Cov.: 33

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.824 AC: 125404 AN: 152226 Hom.: 51841 Cov.: 33 AF XY: 0.826 AC XY: 61489 AN XY: 74428

African (AFR) AF: 0.748 AC: 31083 AN: 41536

American (AMR) AF: 0.822 AC: 12584 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3181 AN: 3472

East Asian (EAS) AF: 0.912 AC: 4698 AN: 5150

South Asian (SAS) AF: 0.828 AC: 3995 AN: 4824

European-Finnish (FIN) AF: 0.880 AC: 9336 AN: 10610

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57670 AN: 68014

Other (OTH) AF: 0.828 AC: 1750 AN: 2114

Alfa AF: 0.821 Hom.: 33137

Bravo AF: 0.817

Asia WGS AF: 0.841 AC: 2924 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.54
DANN	Benign	0.40
PhyloP100		-2.8
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: rs1474587; hg19: chr6-15516709;