rs13198512

Variant names:

• chr6-15519654-C-T
• rs13198512
• NM_004973.4:c.3559-415C>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.3559-415C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,116 control chromosomes in the GnomAD database, including 14,302 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 0.42 (14302 hom., cov: 33)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.3559-415C>T		intron_variant	Intron 17 of 17	ENST00000341776.7	NP_004964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JARID2	ENST00000341776.7	c.3559-415C>T		intron_variant	Intron 17 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.3043-415C>T		intron_variant	Intron 17 of 17	2		ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63847 AN: 151998 Hom.: 14287 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.420 AC: 63891 AN: 152116 Hom.: 14302 Cov.: 33 AF XY: 0.415 AC XY: 30873 AN XY: 74354

African (AFR) AF: 0.283 AC: 11752 AN: 41494

American (AMR) AF: 0.394 AC: 6023 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1976 AN: 3472

East Asian (EAS) AF: 0.234 AC: 1214 AN: 5188

South Asian (SAS) AF: 0.354 AC: 1706 AN: 4824

European-Finnish (FIN) AF: 0.473 AC: 4990 AN: 10542

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34584 AN: 67996

Other (OTH) AF: 0.454 AC: 958 AN: 2112

Alfa AF: 0.483 Hom.: 30922

Bravo AF: 0.408

Asia WGS AF: 0.277 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.50
PhyloP100		0.23
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: rs13198512; hg19: chr6-15519885;