12-45850702-A-T

Variant names:

• chr12-45850702-A-T
• NM_152641.4:c.2579A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152641.4(ARID2):​c.2579A>T​(p.Asn860Ile) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARID2 NM_152641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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
• BP4: Computational evidence support a benign effect (MetaRNN=0.30018002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID2	NM_152641.4	c.2579A>T	p.Asn860Ile	missense_variant	Exon 15 of 21	ENST00000334344.11	NP_689854.2
ARID2	NM_001347839.2	c.2579A>T	p.Asn860Ile	missense_variant	Exon 15 of 20		NP_001334768.1
ARID2	XM_047428489.1	c.2579A>T	p.Asn860Ile	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.2579A>T	p.Asn860Ile	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	Uncertain	0.37
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.034	T;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.028
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D;.;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.066
Sift	Uncertain	0.0010	D;D;D
Sift4G	Benign	0.11	T;T;T
Polyphen		0.022	B;.;B
Vest4		0.58
MutPred		0.48		Gain of catalytic residue at V862 (P = 0);.;.;
MVP		0.28
MPC		0.18
ClinPred		0.43	T
GERP RS		4.7
Varity_R		0.18
gMVP		0.48

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: chr12-46244485;