12-45852633-C-G

Variant names:

• chr12-45852633-C-G
• rs140500006
• NM_152641.4:c.4510C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152641.4(ARID2):​c.4510C>G​(p.Arg1504Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1504Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARID2 NM_152641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• Publications: 6 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID2	NM_152641.4	c.4510C>G	p.Arg1504Gly	missense_variant	Exon 15 of 21	ENST00000334344.11	NP_689854.2
ARID2	NM_001347839.2	c.4510C>G	p.Arg1504Gly	missense_variant	Exon 15 of 20		NP_001334768.1
ARID2	XM_047428489.1	c.4510C>G	p.Arg1504Gly	missense_variant	Exon 15 of 17		XP_047284445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID2	ENST00000334344.11	c.4510C>G	p.Arg1504Gly	missense_variant	Exon 15 of 21	1	NM_152641.4	ENSP00000335044.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T;T;.;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;.;D;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.43	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;.;.;.
PhyloP100		3.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.82	N;N;N;N
REVEL	Benign	0.086
Sift	Uncertain	0.016	D;D;D;T
Sift4G	Benign	0.39	T;T;T;T
Polyphen		0.83	P;.;P;.
Vest4		0.58
MutPred		0.27		Gain of catalytic residue at R1504 (P = 8e-04);.;.;.;
MVP		0.35
MPC		0.22
ClinPred		0.77	D
GERP RS		5.1
PromoterAI		-0.020	Neutral
Varity_R		0.18
gMVP		0.25
Mutation Taster		=88/12	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: rs140500006; hg19: chr12-46246416;