6-15487551-C-G

Variant names:

• chr6-15487551-C-G
• rs2076056
• NM_004973.4:c.906+9C>G

Variant summary

Our verdict is Benign. The variant received -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
• 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: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004973.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JARID2	NM_004973.4	MANE Select	c.906+9C>G		intron	N/A	NP_004964.2
	JARID2	NM_001267040.1		c.390+9C>G		intron	N/A	NP_001253969.1	Q92833-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JARID2	ENST00000341776.7	TSL:1 MANE Select	c.906+9C>G		intron	N/A	ENSP00000341280.2	Q92833-1
	JARID2	ENST00000853926.1		c.906+9C>G		intron	N/A	ENSP00000523985.1
	JARID2	ENST00000853927.1		c.906+9C>G		intron	N/A	ENSP00000523986.1

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

GnomAD2 exomes AF: 0.244 AC: 56805 AN: 233240 AF XY: 0.244

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 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

African (AFR) AF: 0.124 AC: 4053 AN: 32698

American (AMR) AF: 0.217 AC: 9150 AN: 42134

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 7507 AN: 24896

East Asian (EAS) AF: 0.261 AC: 10235 AN: 39258

South Asian (SAS) AF: 0.191 AC: 16071 AN: 83982

European-Finnish (FIN) AF: 0.249 AC: 13169 AN: 52856

Middle Eastern (MID) AF: 0.345 AC: 1949 AN: 5652

European-Non Finnish (NFE) AF: 0.254 AC: 277769 AN: 1094526

Other (OTH) AF: 0.259 AC: 15297 AN: 59162

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

African (AFR) AF: 0.128 AC: 5310 AN: 41532

American (AMR) AF: 0.232 AC: 3546 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1054 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1580 AN: 5160

South Asian (SAS) AF: 0.202 AC: 974 AN: 4830

European-Finnish (FIN) AF: 0.241 AC: 2559 AN: 10598

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17731 AN: 68004

Other (OTH) AF: 0.254 AC: 537 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.17
PhyloP100		-0.32
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: rs2076056; hg19: chr6-15487782; COSMIC: COSV59185208;