NM_004973.4:c.2449-142T>A

Variant names:

• chr6-15504358-T-A
• rs760659
• NM_004973.4:c.2449-142T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004973.4(JARID2):​c.2449-142T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.2449-142T>A		intron_variant	Intron 8 of 17	ENST00000341776.7	NP_004964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JARID2	ENST00000341776.7	c.2449-142T>A		intron_variant	Intron 8 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.1933-142T>A		intron_variant	Intron 8 of 17	2		ENSP00000380478.3
JARID2	ENST00000474854.1	n.53-142T>A		intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000210 AC: 1 AN: 475422 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 254418

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 13276

American (AMR) AF: 0.00 AC: 0 AN: 23728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14256

East Asian (EAS) AF: 0.0000319 AC: 1 AN: 31340

South Asian (SAS) AF: 0.00 AC: 0 AN: 51248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 279278

Other (OTH) AF: 0.00 AC: 0 AN: 26366

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 55192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.86
PhyloP100		-0.32

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: rs760659; hg19: chr6-15504589;