6-15504358-T-C

Variant names:

• chr6-15504358-T-C
• rs760659
• NM_004973.4:c.2449-142T>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.2449-142T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 626,954 control chromosomes in the GnomAD database, including 188,952 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 0.73 (41289 hom., cov: 34)
  • Exomes 𝑓: 0.79 (147663 hom.)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.2449-142T>C		intron_variant	Intron 8 of 17	ENST00000341776.7	NP_004964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JARID2	ENST00000341776.7	c.2449-142T>C		intron_variant	Intron 8 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.1933-142T>C		intron_variant	Intron 8 of 17	2		ENSP00000380478.3
JARID2	ENST00000474854.1	n.53-142T>C		intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110944 AN: 152038 Hom.: 41272 Cov.: 34

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.748

GnomAD4 exome AF: 0.786 AC: 373186 AN: 474798 Hom.: 147663 AF XY: 0.786 AC XY: 199635 AN XY: 254080

African (AFR) AF: 0.570 AC: 7564 AN: 13262

American (AMR) AF: 0.741 AC: 17530 AN: 23666

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 12532 AN: 14236

East Asian (EAS) AF: 0.897 AC: 28098 AN: 31326

South Asian (SAS) AF: 0.772 AC: 39520 AN: 51204

European-Finnish (FIN) AF: 0.828 AC: 26755 AN: 32306

Middle Eastern (MID) AF: 0.774 AC: 2763 AN: 3572

European-Non Finnish (NFE) AF: 0.781 AC: 217826 AN: 278900

Other (OTH) AF: 0.782 AC: 20598 AN: 26326

GnomAD4 genome AF: 0.730 AC: 111004 AN: 152156 Hom.: 41289 Cov.: 34 AF XY: 0.734 AC XY: 54591 AN XY: 74382

African (AFR) AF: 0.578 AC: 23991 AN: 41488

American (AMR) AF: 0.744 AC: 11381 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 3063 AN: 3470

East Asian (EAS) AF: 0.908 AC: 4701 AN: 5180

South Asian (SAS) AF: 0.771 AC: 3723 AN: 4826

European-Finnish (FIN) AF: 0.824 AC: 8726 AN: 10596

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52791 AN: 67978

Other (OTH) AF: 0.747 AC: 1580 AN: 2114

Alfa AF: 0.761 Hom.: 55192

Bravo AF: 0.718

Asia WGS AF: 0.807 AC: 2807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs760659; hg19: chr6-15504589; COSMIC: COSV59198612;