12-45849623-A-T

Variant names:

• chr12-45849623-A-T
• NM_152641.4:c.1759A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152641.4(ARID2):​c.1759A>T​(p.Ser587Cys) variant causes a missense change. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARID2 NM_152641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.51

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]

LOC105369745 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1705288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID2	NM_152641.4	c.1759A>T	p.Ser587Cys	missense_variant	Exon 14 of 21	ENST00000334344.11	NP_689854.2
ARID2	NM_001347839.2	c.1759A>T	p.Ser587Cys	missense_variant	Exon 14 of 20		NP_001334768.1
ARID2	XM_047428489.1	c.1759A>T	p.Ser587Cys	missense_variant	Exon 14 of 17		XP_047284445.1
LOC105369745	XR_944892.3	n.24T>A		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID2	ENST00000334344.11	c.1759A>T	p.Ser587Cys	missense_variant	Exon 14 of 21	1	NM_152641.4	ENSP00000335044.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Uncertain	0.49	T;T;.
Eigen	Benign	-0.00096
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D;.;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.063
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.053	T;T;T
Polyphen		0.41	B;.;.
Vest4		0.35
MutPred		0.37		Loss of disorder (P = 0.0107);.;.;
MVP		0.28
MPC		0.18
ClinPred		0.64	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-46243406;