6-15487551-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004973.4(JARID2):c.906+9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,587,372 control chromosomes in the GnomAD database, including 48,987 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 0.22 (4052 hom., cov: 32)
  • Exomes 𝑓: 0.25 (44935 hom.)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JARID2	NM_004973.4	c.906+9C>G		intron_variant		ENST00000341776.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JARID2	ENST00000341776.7	c.906+9C>G		intron_variant		1	NM_004973.4	P2
JARID2	ENST00000397311.4	c.390+9C>G		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33599 AN: 152090 Hom.: 4052 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.254

GnomAD3 exomes AF: 0.244 AC: 56805 AN: 233240 Hom.: 7169 AF XY: 0.244 AC XY: 30862 AN XY: 126384

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.216

Gnomad ASJ exome AF: 0.319

Gnomad EAS exome AF: 0.317

Gnomad SAS exome AF: 0.191

Gnomad FIN exome AF: 0.251

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.272

GnomAD4 exome AF: 0.247 AC: 355200 AN: 1435164 Hom.: 44935 Cov.: 31 AF XY: 0.247 AC XY: 175581 AN XY: 710470

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.302

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.221 AC: 33612 AN: 152208 Hom.: 4052 Cov.: 32 AF XY: 0.222 AC XY: 16494 AN XY: 74408

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.254

Alfa AF: 0.211 Hom.: 1025

Bravo AF: 0.217

Asia WGS AF: 0.233 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.7
Dann	Benign	0.17

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: rs2076056; hg19: chr6-15487782; COSMIC: COSV59185208;