chr12-45849623-A-G

Position:

chr12-45849623-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBS1BS2

The NM_152641.4(ARID2):c.1759A>G(p.Ser587Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00107 in 1,613,622 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 15 hom. )

Consequence

ARID2
NM_152641.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 5.51

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 links:

LOC105369745 (HGNC:):

LOC105369745 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ARID2. . Gene score misZ 2.7332 (greater than the threshold 3.09). Trascript score misZ 4.4744 (greater than threshold 3.09). GenCC has associacion of gene with Coffin-Siris syndrome 6, Coffin-Siris syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032149851).

BP6

Variant 12-45849623-A-G is Benign according to our data. Variant chr12-45849623-A-G is described in ClinVar as [Benign]. Clinvar id is 133559.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00125 (190/152316) while in subpopulation EAS AF= 0.0274 (142/5188). AF 95% confidence interval is 0.0237. There are 4 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 190 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARID2	NM_152641.4 linkuse as main transcript	c.1759A>G	p.Ser587Gly	missense_variant	14/21	ENST00000334344.11	NP_689854.2
LOC105369745	XR_944892.3 linkuse as main transcript	n.24T>C		non_coding_transcript_exon_variant	1/4
ARID2	NM_001347839.2 linkuse as main transcript	c.1759A>G	p.Ser587Gly	missense_variant	14/20		NP_001334768.1
ARID2	XM_047428489.1 linkuse as main transcript	c.1759A>G	p.Ser587Gly	missense_variant	14/17		XP_047284445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID2	ENST00000334344.11 linkuse as main transcript	c.1759A>G	p.Ser587Gly	missense_variant	14/21	1	NM_152641.4	ENSP00000335044	P1	Q68CP9-1
ARID2	ENST00000422737.7 linkuse as main transcript	c.1759A>G	p.Ser587Gly	missense_variant	14/20	1		ENSP00000415650
ARID2	ENST00000444670.5 linkuse as main transcript	c.607A>G	p.Ser203Gly	missense_variant	6/13	1		ENSP00000397307
ARID2	ENST00000479608.5 linkuse as main transcript	c.*309A>G		3_prime_UTR_variant, NMD_transcript_variant	8/15	1		ENSP00000514783

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

191

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.0273

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00262

AC:

659

AN:

251174

Hom.:

AF XY:

0.00259

AC XY:

351

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00734

Gnomad EAS exome

AF:

0.0287

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.00105

AC:

1535

AN:

1461306

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

799

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00789

Gnomad4 EAS exome

AF:

0.0256

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152316

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.0274

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00177

Hom.:

Bravo

AF:

0.00174

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00256

AC:

311

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.034

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

T;.;T

MetaRNN

Benign

0.0032

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.24

N;N;N

REVEL

Benign

0.025

Sift

Benign

0.041

D;T;T

Sift4G

Benign

0.37

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.19

MVP

0.34

MPC

0.12

ClinPred

0.035

GERP RS

4.6

Varity_R

0.11

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over