dbSNP rs17619975: JARID2:c.182-7703T>G (chr6-15402521-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_004973.4(JARID2):c.182-7703T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0317 in 152,252 control chromosomes in the GnomAD database, including 79 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 0.032 ( 79 hom., cov: 32)

Consequence

JARID2
NM_004973.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.532

Publications

3 publications found

Variant links:

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

JARID2 links:

ENSG00000309943 (HGNC:):

ENSG00000309943 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0317 (4827/152252) while in subpopulation SAS AF = 0.0528 (255/4830). AF 95% confidence interval is 0.0475. There are 79 homozygotes in GnomAd4. There are 2329 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 4827 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4 link	c.182-7703T>G		intron_variant	Intron 2 of 17	ENST00000341776.7	NP_004964.2	Q92833-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
JARID2	ENST00000341776.7 link	c.182-7703T>G	intron_variant	Intron 2 of 17	1	NM_004973.4	ENSP00000341280.2	Q92833-1
JARID2	ENST00000397311.4 link	c.-335-7703T>G	intron_variant	Intron 2 of 17	2		ENSP00000380478.3	Q92833-3
ENSG00000309943	ENST00000846078.1 link	n.253+938A>C	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0317

AC:

4830

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0403

Gnomad AMI

AF:

0.0791

Gnomad AMR

AF:

0.0172

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.0229

Gnomad SAS

AF:

0.0530

Gnomad FIN

AF:

0.0207

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0301

Gnomad OTH

AF:

0.0253

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

GnomAD4 genome

AF:

0.0317

AC:

4827

AN:

152252

Hom.:

Cov.:

AF XY:

0.0313

AC XY:

2329

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0402

AC:

1670

AN:

41550

American (AMR)

AF:

0.0171

AC:

262

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0337

AC:

117

AN:

3468

East Asian (EAS)

AF:

0.0230

AC:

119

AN:

5180

South Asian (SAS)

AF:

0.0528

AC:

255

AN:

4830

European-Finnish (FIN)

AF:

0.0207

AC:

220

AN:

10616

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0301

AC:

2049

AN:

67998

Other (OTH)

AF:

0.0251

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

239

477

716

954

1193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0340

Hom.:

Bravo

AF:

0.0317

Asia WGS

AF:

0.0380

AC:

133

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.9

(source)

DANN

Benign

0.46

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over