rs149755754

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_152641.4(ARID2):c.1472C>G(p.Thr491Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000971 in 1,613,518 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

ARID2
NM_152641.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 4.75

Publications

7 publications found

Variant links:

Genes affected

ARID2 (HGNC:18037): (AT-rich interaction domain 2) This gene encodes a member of the AT-rich interactive domain (ARID)-containing family of DNA-binding proteins. Members of the ARID family have roles in embryonic patterning, cell lineage gene regulation, cell cycle control, transcriptional regulation and chromatin structure modification. This protein functions as a subunit of the polybromo- and BRG1-associated factor or PBAF (SWI/SNF-B) chromatin remodeling complex which facilitates ligand-dependent transcriptional activation by nuclear receptors. Mutations in this gene are associated with hepatocellular carcinomas. A pseudogene of this gene is found on chromosome1. [provided by RefSeq, Dec 2016]

ARID2 Gene-Disease associations (from GenCC):

Coffin-Siris syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Illumina, ClinGen
Coffin-Siris syndrome 6
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ARID2 links:

LOC105369745 (HGNC:):

LOC105369745 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022067517).

BP6

Variant 12-45839470-C-G is Benign according to our data. Variant chr12-45839470-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 133558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000723 (110/152248) while in subpopulation NFE AF = 0.00143 (97/68010). AF 95% confidence interval is 0.0012. There are 0 homozygotes in GnomAd4. There are 55 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 110 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152641.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID2	NM_152641.4	MANE Select	c.1472C>G	p.Thr491Ser	missense	Exon 11 of 21	NP_689854.2
	ARID2	NM_001347839.2		c.1472C>G	p.Thr491Ser	missense	Exon 11 of 20	NP_001334768.1	F8WCU9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARID2	ENST00000334344.11	TSL:1 MANE Select	c.1472C>G	p.Thr491Ser	missense	Exon 11 of 21	ENSP00000335044.6	Q68CP9-1
ARID2	ENST00000422737.7	TSL:1	c.1472C>G	p.Thr491Ser	missense	Exon 11 of 20	ENSP00000415650.3	F8WCU9
ARID2	ENST00000444670.5	TSL:1	c.317C>G	p.Thr106Ser	missense	Exon 3 of 13	ENSP00000397307.2	F8W108

Frequencies

GnomAD3 genomes

AF:

0.000723

AC:

110

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000686

AC:

172

AN:

250630

AF XY:

0.000694

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00116

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000996

AC:

1456

AN:

1461270

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

737

AN XY:

726928

show subpopulations

African (AFR)

AF:

0.0000897

AC:

AN:

33442

American (AMR)

AF:

0.000135

AC:

AN:

44608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.000882

AC:

AN:

86120

European-Finnish (FIN)

AF:

0.000318

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00116

AC:

1286

AN:

1111768

Other (OTH)

AF:

0.00111

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

149

224

298

373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000723

AC:

110

AN:

152248

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41548

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.000622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00143

AC:

AN:

68010

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00108

Hom.:

Bravo

AF:

0.000756

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000708

AC:

EpiCase

AF:

0.00153

EpiControl

AF:

0.000889

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

ARID2-related disorder (1)

Coffin-Siris syndrome 6 (1)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.011

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.52

M_CAP

Benign

0.0020

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.4

PhyloP100

4.8

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.39

REVEL

Benign

0.069

Sift

Benign

0.69

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.14

MutPred

0.22

Gain of catalytic residue at T493 (P = 0.0103)

MVP

0.27

MPC

0.11

ClinPred

0.032

GERP RS

4.3

Varity_R

0.079

gMVP

0.12

Mutation Taster

=97/3

polymorphism

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over