rs11962776

Variant names:

• chr6-15259922-C-A
• rs11962776
• NM_004973.4:c.45+13338C>A

Variant summary

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

Score: -12 - Benign

-12

BP4_StrongBA1

The NM_004973.4(JARID2):​c.45+13338C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,004 control chromosomes in the GnomAD database, including 2,381 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 0.15 (2381 hom., cov: 32)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.45+13338C>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.45+13338C>A		intron_variant	Intron 1 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.-472+10958C>A		intron_variant	Intron 1 of 17	2		ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22590 AN: 151886 Hom.: 2376 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0837

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.149 AC: 22619 AN: 152004 Hom.: 2381 Cov.: 32 AF XY: 0.148 AC XY: 11033 AN XY: 74306

African (AFR) AF: 0.297 AC: 12325 AN: 41430

American (AMR) AF: 0.150 AC: 2291 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 271 AN: 3470

East Asian (EAS) AF: 0.103 AC: 532 AN: 5190

South Asian (SAS) AF: 0.0198 AC: 95 AN: 4810

European-Finnish (FIN) AF: 0.101 AC: 1064 AN: 10530

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0837 AC: 5690 AN: 67980

Other (OTH) AF: 0.137 AC: 289 AN: 2108

Alfa AF: 0.0960 Hom.: 465

Bravo AF: 0.161

Asia WGS AF: 0.0730 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.4
DANN	Benign	0.57
PhyloP100		-0.072
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: rs11962776; hg19: chr6-15260153;