6-15513513-G-T

Variant summary

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

The NM_004973.4(JARID2):c.3450+91G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,255,406 control chromosomes in the GnomAD database, including 50,554 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 (4887 hom., cov: 34)
  • Exomes 𝑓: 0.28 (45667 hom.)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JARID2	NM_004973.4	c.3450+91G>T		intron_variant		ENST00000341776.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JARID2	ENST00000341776.7	c.3450+91G>T		intron_variant		1	NM_004973.4	P2
JARID2	ENST00000397311.4	c.2934+91G>T		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35229 AN: 152064 Hom.: 4888 Cov.: 34

Gnomad AFR AF: 0.0846

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.281 AC: 310235 AN: 1103224 Hom.: 45667 AF XY: 0.284 AC XY: 154227 AN XY: 543236

Gnomad4 AFR exome AF: 0.0769

Gnomad4 AMR exome AF: 0.314

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.471

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.371

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.271

GnomAD4 genome AF: 0.231 AC: 35228 AN: 152182 Hom.: 4887 Cov.: 34 AF XY: 0.241 AC XY: 17939 AN XY: 74380

Gnomad4 AFR AF: 0.0845

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.219

Alfa AF: 0.137 Hom.: 288

Bravo AF: 0.217

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.62
Dann	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs9396589; hg19: chr6-15513744; COSMIC: COSV59201385;