rs13193457

Variant names:

• chr6-15345774-C-A
• rs13193457
• NM_004973.4:c.46-28343C>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.46-28343C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 152,120 control chromosomes in the GnomAD database, including 700 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 0.091 (700 hom., cov: 32)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.46-28343C>A		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.46-28343C>A		intron_variant	Intron 1 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.-471-28343C>A		intron_variant	Intron 1 of 17	2		ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13885 AN: 152002 Hom.: 700 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0821

Gnomad ASJ AF: 0.0950

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0717

Gnomad OTH AF: 0.0837

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

GnomAD4 genome AF: 0.0913 AC: 13887 AN: 152120 Hom.: 700 Cov.: 32 AF XY: 0.0945 AC XY: 7028 AN XY: 74358

African (AFR) AF: 0.109 AC: 4511 AN: 41494

American (AMR) AF: 0.0822 AC: 1255 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0950 AC: 330 AN: 3472

East Asian (EAS) AF: 0.196 AC: 1010 AN: 5164

South Asian (SAS) AF: 0.0265 AC: 128 AN: 4828

European-Finnish (FIN) AF: 0.144 AC: 1517 AN: 10568

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0717 AC: 4876 AN: 68002

Other (OTH) AF: 0.0829 AC: 175 AN: 2112

Alfa AF: 0.0749 Hom.: 1455

Bravo AF: 0.0880

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.069
DANN	Benign	0.73
PhyloP100		-1.6
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: rs13193457; hg19: chr6-15346005;