6-15468645-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_004973.4(JARID2):c.597C>T(p.Thr199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00691 in 1,613,882 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T199T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0054 (4 hom., cov: 30)
  • Exomes 𝑓: 0.0071 (59 hom.)
• Consequence: JARID2 NM_004973.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.90

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 6-15468645-C-T is Benign according to our data. Variant chr6-15468645-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 788355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.9 with no splicing effect.
• BS2: High AC in GnomAd at 816 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JARID2	NM_004973.4	c.597C>T	p.Thr199=	synonymous_variant	5/18	ENST00000341776.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JARID2	ENST00000341776.7	c.597C>T	p.Thr199=	synonymous_variant	5/18	1	NM_004973.4	P2
JARID2	ENST00000397311.4	c.81C>T	p.Thr27=	synonymous_variant	5/18	2		A2

Frequencies

GnomAD3 genomes AF: 0.00537 AC: 816 AN: 152034 Hom.: 4 Cov.: 30

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00690

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00613 AC: 1541 AN: 251236 Hom.: 14 AF XY: 0.00629 AC XY: 854 AN XY: 135784

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00190

Gnomad FIN exome AF: 0.0267

Gnomad NFE exome AF: 0.00709

Gnomad OTH exome AF: 0.00636

GnomAD4 exome AF: 0.00707 AC: 10335 AN: 1461730 Hom.: 59 Cov.: 32 AF XY: 0.00699 AC XY: 5081 AN XY: 727154

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00145

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00197

Gnomad4 FIN exome AF: 0.0232

Gnomad4 NFE exome AF: 0.00763

Gnomad4 OTH exome AF: 0.00560

GnomAD4 genome AF: 0.00536 AC: 816 AN: 152152 Hom.: 4 Cov.: 30 AF XY: 0.00573 AC XY: 426 AN XY: 74382

Gnomad4 AFR AF: 0.00125

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0232

Gnomad4 NFE AF: 0.00690

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00356 Hom.: 158

EpiCase AF: 0.00764

EpiControl AF: 0.00522

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	JARID2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	12
Dann	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs7768621; hg19: chr6-15468876;