12-45891802-G-C

Variant names:

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.4945G>C(p.Val1649Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000665 in 1,614,112 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 9 hom. )

Consequence

ARID2
NM_152641.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 9.32

Publications

9 publications found

Variant links:

COSMIC-nc: COSV57606957

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

ARID2 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=0.012111098).

BP6

Variant 12-45891802-G-C is Benign according to our data. Variant chr12-45891802-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 133572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000473 (72/152264) while in subpopulation SAS AF = 0.00477 (23/4820). AF 95% confidence interval is 0.00326. There are 0 homozygotes in GnomAd4. There are 45 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 72 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID2	NM_152641.4 link	c.4945G>C	p.Val1649Leu	missense_variant	Exon 17 of 21	ENST00000334344.11	NP_689854.2
ARID2	NM_001347839.2 link	c.4945G>C	p.Val1649Leu	missense_variant	Exon 17 of 20		NP_001334768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID2	ENST00000334344.11 link	c.4945G>C	p.Val1649Leu	missense_variant	Exon 17 of 21	1	NM_152641.4	ENSP00000335044.6

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00109

AC:

275

AN:

251254

AF XY:

0.00140

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000828

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000685

AC:

1002

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000865

AC XY:

629

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33480

American (AMR)

AF:

0.000559

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000651

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00499

AC:

430

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00468

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000404

AC:

449

AN:

1111988

Other (OTH)

AF:

0.000778

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

122

183

244

305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000473

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41540

American (AMR)

AF:

0.000458

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00477

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68024

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.000812

Hom.:

Bravo

AF:

0.000400

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00134

AC:

163

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.00148

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ARID2: BS2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

T;T;.;.

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;.;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;.;.;.

PhyloP100

9.3

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.97

N;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.10

T;T;T;T

Sift4G

Uncertain

0.051

T;T;T;D

Vest4

0.74

ClinPred

0.054

GERP RS

5.2

PromoterAI

0.015

Neutral

(source)

Varity_R

0.32

gMVP

0.49

Mutation Taster

=68/32

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over