chr12-45852423-G-C

Position:

• chr12-45852423-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The ENST00000334344.11(ARID2):​c.4300G>C​(p.Ala1434Pro) 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. 14/21 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. A1434S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARID2 ENST00000334344.11 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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=0.13250124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID2	NM_152641.4	c.4300G>C	p.Ala1434Pro	missense_variant	15/21	ENST00000334344.11	NP_689854.2
ARID2	NM_001347839.2	c.4300G>C	p.Ala1434Pro	missense_variant	15/20		NP_001334768.1
ARID2	XM_047428489.1	c.4300G>C	p.Ala1434Pro	missense_variant	15/17		XP_047284445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID2	ENST00000334344.11	c.4300G>C	p.Ala1434Pro	missense_variant	15/21	1	NM_152641.4	ENSP00000335044	P1

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	0.098
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;T;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.065
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.71	T;.;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N;.;.;.
MutationTaster	Benign	0.98	D;D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.20	N;N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Benign	0.23	T;T;T;D
Polyphen		0.61	P;.;P;.
Vest4		0.23
MutPred		0.20		Gain of relative solvent accessibility (P = 0.0166);.;.;.;
MVP		0.33
MPC		0.16
ClinPred		0.20	T
GERP RS		1.0
Varity_R		0.11
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-46246206;