NM_004973.4:c.494-5378T>C

Variant names:

• chr6-15463164-T-C
• rs2237138
• NM_004973.4:c.494-5378T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004973.4(JARID2):​c.494-5378T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,084 control chromosomes in the GnomAD database, including 4,184 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 (4184 hom., cov: 31)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.494-5378T>C		intron_variant	Intron 4 of 17	ENST00000341776.7	NP_004964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JARID2	ENST00000341776.7	c.494-5378T>C		intron_variant	Intron 4 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.-23-5378T>C		intron_variant	Intron 4 of 17	2		ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33888 AN: 151966 Hom.: 4181 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.223 AC: 33922 AN: 152084 Hom.: 4184 Cov.: 31 AF XY: 0.225 AC XY: 16757 AN XY: 74322

African (AFR) AF: 0.117 AC: 4866 AN: 41518

American (AMR) AF: 0.271 AC: 4144 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1052 AN: 3464

East Asian (EAS) AF: 0.283 AC: 1463 AN: 5164

South Asian (SAS) AF: 0.201 AC: 970 AN: 4824

European-Finnish (FIN) AF: 0.270 AC: 2849 AN: 10560

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.261 AC: 17731 AN: 67968

Other (OTH) AF: 0.250 AC: 527 AN: 2108

Alfa AF: 0.241 Hom.: 615

Bravo AF: 0.221

Asia WGS AF: 0.226 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.38
PhyloP100		-2.1
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: rs2237138; hg19: chr6-15463395;