6-15519145-T-C

Variant names:

• chr6-15519145-T-C
• rs13213814
• NM_004973.4:c.3559-924T>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.3559-924T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,118 control chromosomes in the GnomAD database, including 3,300 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 0.19 (3300 hom., cov: 32)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.72
• Publications: 0 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.3559-924T>C		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.3559-924T>C		intron_variant	Intron 17 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.3043-924T>C		intron_variant	Intron 17 of 17	2		ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29624 AN: 152000 Hom.: 3294 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.195 AC: 29631 AN: 152118 Hom.: 3300 Cov.: 32 AF XY: 0.187 AC XY: 13879 AN XY: 74360

African (AFR) AF: 0.131 AC: 5437 AN: 41504

American (AMR) AF: 0.163 AC: 2494 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 996 AN: 3464

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5168

South Asian (SAS) AF: 0.116 AC: 557 AN: 4818

European-Finnish (FIN) AF: 0.171 AC: 1816 AN: 10592

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17524 AN: 67968

Other (OTH) AF: 0.196 AC: 413 AN: 2108

Alfa AF: 0.222 Hom.: 540

Bravo AF: 0.194

Asia WGS AF: 0.0590 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.48
DANN	Benign	0.17
PhyloP100		-2.7
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: rs13213814; hg19: chr6-15519376;