chr6-15516402-G-A

Variant names:

• chr6-15516402-G-A
• rs742102
• NM_004973.4:c.3451-759G>A

Variant summary

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

The NM_004973.4(JARID2):​c.3451-759G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 152,270 control chromosomes in the GnomAD database, including 132 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 0.033 (132 hom., cov: 33)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 0 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 (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.3451-759G>A		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.3451-759G>A		intron_variant	Intron 16 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.2935-759G>A		intron_variant	Intron 16 of 17	2		ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.0332 AC: 5058 AN: 152152 Hom.: 130 Cov.: 33

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0241

Gnomad ASJ AF: 0.0475

Gnomad EAS AF: 0.0954

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0370

Gnomad OTH AF: 0.0354

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

GnomAD4 genome AF: 0.0333 AC: 5064 AN: 152270 Hom.: 132 Cov.: 33 AF XY: 0.0355 AC XY: 2645 AN XY: 74448

African (AFR) AF: 0.0107 AC: 446 AN: 41556

American (AMR) AF: 0.0241 AC: 369 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0475 AC: 165 AN: 3472

East Asian (EAS) AF: 0.0950 AC: 491 AN: 5166

South Asian (SAS) AF: 0.113 AC: 546 AN: 4826

European-Finnish (FIN) AF: 0.0403 AC: 427 AN: 10602

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0371 AC: 2521 AN: 68028

Other (OTH) AF: 0.0383 AC: 81 AN: 2114

Alfa AF: 0.0362 Hom.: 169

Bravo AF: 0.0290

Asia WGS AF: 0.0980 AC: 345 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	0.16
DANN	Benign	0.68
PhyloP100		-0.14
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: rs742102; hg19: chr6-15516633;