rs909626

Variant names:

• chr6-15517453-C-T
• rs909626
• NM_004973.4:c.3558+185C>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+185C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,158 control chromosomes in the GnomAD database, including 1,579 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 0.14 (1579 hom., cov: 33)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.3558+185C>T		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+185C>T		intron_variant	Intron 17 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.3042+185C>T		intron_variant	Intron 17 of 17	2		ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21469 AN: 152040 Hom.: 1573 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.141 AC: 21498 AN: 152158 Hom.: 1579 Cov.: 33 AF XY: 0.140 AC XY: 10441 AN XY: 74386

African (AFR) AF: 0.124 AC: 5162 AN: 41500

American (AMR) AF: 0.180 AC: 2758 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 758 AN: 3468

East Asian (EAS) AF: 0.138 AC: 711 AN: 5158

South Asian (SAS) AF: 0.152 AC: 733 AN: 4824

European-Finnish (FIN) AF: 0.0836 AC: 886 AN: 10604

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9968 AN: 67994

Other (OTH) AF: 0.178 AC: 377 AN: 2114

Alfa AF: 0.156 Hom.: 2967

Bravo AF: 0.147

Asia WGS AF: 0.151 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.63
PhyloP100		-0.33
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: rs909626; hg19: chr6-15517684;