rs2076056

Variant names:

• chr6-15487551-C-A
• rs2076056
• NM_004973.4:c.906+9C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-15487551-C-A
• chr6-15487551-C-G
• chr6-15487551-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004973.4(JARID2):​c.906+9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000488 in 1,435,680 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 6 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.906+9C>A		intron_variant	Intron 6 of 17	ENST00000341776.7	NP_004964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JARID2	ENST00000341776.7	c.906+9C>A		intron_variant	Intron 6 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.390+9C>A		intron_variant	Intron 6 of 17	2		ENSP00000380478.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000488 AC: 7 AN: 1435680 Hom.: 0 Cov.: 31 AF XY: 0.00000563 AC XY: 4 AN XY: 710724

African (AFR) AF: 0.000153 AC: 5 AN: 32710

American (AMR) AF: 0.00 AC: 0 AN: 42180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24910

East Asian (EAS) AF: 0.00 AC: 0 AN: 39266

South Asian (SAS) AF: 0.00 AC: 0 AN: 84016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094900

Other (OTH) AF: 0.0000338 AC: 2 AN: 59178

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1025

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.27
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: rs2076056; hg19: chr6-15487782;