6-15513513-G-T

Variant names:

• chr6-15513513-G-T
• rs9396589
• NM_004973.4:c.3450+91G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.92).
• 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 rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.3450+91G>T		intron_variant	Intron 16 of 17	ENST00000341776.7	NP_004964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JARID2	ENST00000341776.7	c.3450+91G>T		intron_variant	Intron 16 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.2934+91G>T		intron_variant	Intron 16 of 17	2		ENSP00000380478.3

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

African (AFR) AF: 0.0769 AC: 2000 AN: 26014

American (AMR) AF: 0.314 AC: 7341 AN: 23416

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 4920 AN: 17956

East Asian (EAS) AF: 0.471 AC: 16928 AN: 35910

South Asian (SAS) AF: 0.349 AC: 21377 AN: 61308

European-Finnish (FIN) AF: 0.371 AC: 15963 AN: 42980

Middle Eastern (MID) AF: 0.199 AC: 867 AN: 4350

European-Non Finnish (NFE) AF: 0.270 AC: 227951 AN: 843758

Other (OTH) AF: 0.271 AC: 12888 AN: 47532

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

African (AFR) AF: 0.0845 AC: 3511 AN: 41558

American (AMR) AF: 0.279 AC: 4265 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 984 AN: 3472

East Asian (EAS) AF: 0.427 AC: 2193 AN: 5136

South Asian (SAS) AF: 0.349 AC: 1688 AN: 4834

European-Finnish (FIN) AF: 0.378 AC: 3997 AN: 10586

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17838 AN: 67980

Other (OTH) AF: 0.219 AC: 464 AN: 2114

Alfa AF: 0.136 Hom.: 291

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
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9396589; hg19: chr6-15513744; COSMIC: COSV59201385;