chr12-45817793-C-T

Variant names:

• chr12-45817793-C-T
• rs1555149372
• NM_152641.4:c.542C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152641.4(ARID2):​c.542C>T​(p.Thr181Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARID2 NM_152641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.761

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.542C>T	p.Thr181Ile	missense	Exon 5 of 21	NP_689854.2
	ARID2	NM_001347839.2		c.542C>T	p.Thr181Ile	missense	Exon 5 of 20	NP_001334768.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID2	ENST00000334344.11	TSL:1 MANE Select	c.542C>T	p.Thr181Ile	missense	Exon 5 of 21	ENSP00000335044.6
	ARID2	ENST00000422737.7	TSL:1	c.542C>T	p.Thr181Ile	missense	Exon 5 of 20	ENSP00000415650.3
	ARID2	ENST00000851072.1		c.542C>T	p.Thr181Ile	missense	Exon 5 of 21	ENSP00000521133.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.056	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.51	T
PhyloP100		6.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-4.4	D
REVEL	Uncertain	0.40
Sift	Benign	0.048	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.36		Gain of catalytic residue at L182 (P = 0.0024)
MVP		0.69
MPC		2.3
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.37
gMVP		0.86
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

dbSNP: rs1555149372; hg19: chr12-46211576;