12-45852615-G-T

Variant summary

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

The NM_152641.4(ARID2):c.4492G>T(p.Ala1498Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A1498T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ARID2 NM_152641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44

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 where missense usually causes diseases, ARID2
• BP4: Computational evidence support a benign effect (MetaRNN=0.08390546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID2	NM_152641.4	c.4492G>T	p.Ala1498Ser	missense_variant	15/21	ENST00000334344.11
ARID2	NM_001347839.2	c.4492G>T	p.Ala1498Ser	missense_variant	15/20
ARID2	XM_047428489.1	c.4492G>T	p.Ala1498Ser	missense_variant	15/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID2	ENST00000334344.11	c.4492G>T	p.Ala1498Ser	missense_variant	15/21	1	NM_152641.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461852 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.015	T;T;.;.
Eigen	Benign	-0.082
Eigen_PC	Benign	0.098
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T;.;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.084	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;.;.;.
MutationTaster	Benign	0.99	N;N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.22	N;N;N;N
REVEL	Benign	0.039
Sift	Uncertain	0.019	D;D;D;T
Sift4G	Benign	0.86	T;T;T;T
Polyphen		0.0090	B;.;B;.
Vest4		0.14
MutPred		0.15		Gain of phosphorylation at A1498 (P = 0.0132);.;.;.;
MVP		0.22
MPC		0.13
ClinPred		0.43	T
GERP RS		4.6
Varity_R		0.087
gMVP		0.13

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: chr12-46246398;