rs9654600

Variant names:

• chr6-15513882-T-A
• rs9654600
• NM_004973.4:c.3450+460T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-15513882-T-A
• chr6-15513882-T-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.3450+460T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,316 control chromosomes in the GnomAD database, including 1,234 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 0.12 (1234 hom., cov: 34)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 2 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: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• 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 (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004973.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JARID2	NM_004973.4	MANE Select	c.3450+460T>A		intron	N/A	NP_004964.2
	JARID2	NM_001267040.1		c.2934+460T>A		intron	N/A	NP_001253969.1	Q92833-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JARID2	ENST00000341776.7	TSL:1 MANE Select	c.3450+460T>A		intron	N/A	ENSP00000341280.2	Q92833-1
	JARID2	ENST00000853926.1		c.3450+460T>A		intron	N/A	ENSP00000523985.1
	JARID2	ENST00000853927.1		c.3450+460T>A		intron	N/A	ENSP00000523986.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17539 AN: 152198 Hom.: 1237 Cov.: 34

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0688

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.115 AC: 17556 AN: 152316 Hom.: 1234 Cov.: 34 AF XY: 0.115 AC XY: 8561 AN XY: 74478

African (AFR) AF: 0.181 AC: 7521 AN: 41556

American (AMR) AF: 0.128 AC: 1954 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0688 AC: 239 AN: 3472

East Asian (EAS) AF: 0.235 AC: 1216 AN: 5178

South Asian (SAS) AF: 0.119 AC: 575 AN: 4832

European-Finnish (FIN) AF: 0.0589 AC: 626 AN: 10626

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0748 AC: 5091 AN: 68024

Other (OTH) AF: 0.115 AC: 244 AN: 2114

Alfa AF: 0.0157 Hom.: 5

Bravo AF: 0.125

Asia WGS AF: 0.172 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.1
DANN	Benign	0.44
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs9654600; hg19: chr6-15514113;