6-15267820-C-T

Variant names:

• chr6-15267820-C-T
• rs7766973
• NM_004973.4:c.45+21236C>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.45+21236C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,818 control chromosomes in the GnomAD database, including 16,803 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 0.46 (16803 hom., cov: 31)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.45+21236C>T		intron_variant	Intron 1 of 17	ENST00000341776.7	NP_004964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JARID2	ENST00000341776.7	c.45+21236C>T		intron_variant	Intron 1 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.-472+18856C>T		intron_variant	Intron 1 of 17	2		ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69808 AN: 151700 Hom.: 16768 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.460 AC: 69893 AN: 151818 Hom.: 16803 Cov.: 31 AF XY: 0.465 AC XY: 34495 AN XY: 74178

African (AFR) AF: 0.607 AC: 25122 AN: 41370

American (AMR) AF: 0.393 AC: 5998 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1590 AN: 3468

East Asian (EAS) AF: 0.409 AC: 2109 AN: 5156

South Asian (SAS) AF: 0.479 AC: 2305 AN: 4814

European-Finnish (FIN) AF: 0.446 AC: 4699 AN: 10526

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26592 AN: 67930

Other (OTH) AF: 0.424 AC: 893 AN: 2106

Alfa AF: 0.411 Hom.: 16486

Bravo AF: 0.461

Asia WGS AF: 0.410 AC: 1426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.38
PhyloP100		0.28
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: rs7766973; hg19: chr6-15268051;