rs909626

chr6-15517453-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
JARID2	NM_004973.4	c.3558+185C>T		intron_variant		ENST00000341776.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JARID2	ENST00000341776.7	c.3558+185C>T		intron_variant		1	NM_004973.4	P2
JARID2	ENST00000397311.4	c.3042+185C>T		intron_variant		2		A2

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

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.0836

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.178

Alfa AF: 0.156 Hom.: 2246

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs909626; hg19: chr6-15517684;