6-15456939-G-A

Position:

• chr6-15456939-G-A

Variant summary

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

The NM_004973.4(JARID2):​c.493+4764G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 136,922 control chromosomes in the GnomAD database, including 4,816 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 0.27 (4816 hom., cov: 23)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JARID2	NM_004973.4	c.493+4764G>A		intron_variant		ENST00000341776.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JARID2	ENST00000341776.7	c.493+4764G>A		intron_variant		1	NM_004973.4	P2
JARID2	ENST00000397311.4	c.-24+4764G>A		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 36526 AN: 136832 Hom.: 4815 Cov.: 23

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.388

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.267 AC: 36556 AN: 136922 Hom.: 4816 Cov.: 23 AF XY: 0.271 AC XY: 17729 AN XY: 65334

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.295

Alfa AF: 0.235 Hom.: 1780

Bravo AF: 0.260

Asia WGS AF: 0.275 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.70

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: rs2299043; hg19: chr6-15457170; COSMIC: COSV59196004;