chr6-15257508-T-C

Variant names:

• chr6-15257508-T-C
• rs13208655
• NM_004973.4:c.45+10924T>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.45+10924T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,050 control chromosomes in the GnomAD database, including 22,666 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 0.54 (22666 hom., cov: 32)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.45+10924T>C		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+10924T>C		intron_variant	Intron 1 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.-472+8544T>C		intron_variant	Intron 1 of 17	2		ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82324 AN: 151932 Hom.: 22626 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.542 AC: 82412 AN: 152050 Hom.: 22666 Cov.: 32 AF XY: 0.546 AC XY: 40571 AN XY: 74308

African (AFR) AF: 0.641 AC: 26578 AN: 41450

American (AMR) AF: 0.490 AC: 7493 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1729 AN: 3472

East Asian (EAS) AF: 0.564 AC: 2913 AN: 5166

South Asian (SAS) AF: 0.556 AC: 2678 AN: 4818

European-Finnish (FIN) AF: 0.535 AC: 5659 AN: 10584

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33621 AN: 67966

Other (OTH) AF: 0.500 AC: 1056 AN: 2112

Alfa AF: 0.535 Hom.: 2731

Bravo AF: 0.540

Asia WGS AF: 0.517 AC: 1799 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	1.0
DANN	Benign	0.43
PhyloP100		-1.3
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: rs13208655; hg19: chr6-15257739;