12-45849764-C-T

Variant names:

• chr12-45849764-C-T
• rs368420427
• NM_152641.4:c.1900C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152641.4(ARID2):​c.1900C>T​(p.Pro634Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. P634A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARID2 NM_152641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• Publications: 1 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: Orphanet, Illumina, ClinGen
• Coffin-Siris syndrome 6

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

LOC105369745 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21667188).

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.1900C>T	p.Pro634Ser	missense	Exon 14 of 21	NP_689854.2
	ARID2	NM_001347839.2		c.1900C>T	p.Pro634Ser	missense	Exon 14 of 20	NP_001334768.1	F8WCU9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARID2	ENST00000334344.11	TSL:1 MANE Select	c.1900C>T	p.Pro634Ser	missense	Exon 14 of 21	ENSP00000335044.6	Q68CP9-1
	ARID2	ENST00000422737.7	TSL:1	c.1900C>T	p.Pro634Ser	missense	Exon 14 of 20	ENSP00000415650.3	F8WCU9
	ARID2	ENST00000444670.5	TSL:1	c.745C>T	p.Pro249Ser	missense	Exon 6 of 13	ENSP00000397307.2	F8W108

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.022
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		2.0
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.12
Sift	Benign	0.055	T
Sift4G	Benign	0.27	T
Polyphen		0.38	B
Vest4		0.33
MutPred		0.24		Gain of catalytic residue at V630 (P = 0.0031)
MVP		0.12
MPC		0.13
ClinPred		0.74	D
GERP RS		5.9
Varity_R		0.10
gMVP		0.23
Mutation Taster		=90/10	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: rs368420427; hg19: chr12-46243547;