12-45729906-C-T

Position:

• chr12-45729906-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP2 PP3_Moderate

The NM_152641.4(ARID2):​c.70C>T​(p.Arg24Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARID2 NM_152641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.96

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 5 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.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARID2	NM_152641.4	c.70C>T	p.Arg24Trp	missense_variant	1/21	ENST00000334344.11
ARID2	NM_001347839.2	c.70C>T	p.Arg24Trp	missense_variant	1/20
ARID2	XM_047428489.1	c.70C>T	p.Arg24Trp	missense_variant	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARID2	ENST00000334344.11	c.70C>T	p.Arg24Trp	missense_variant	1/21	1	NM_152641.4	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458016 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725128

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

ARID2: PM2, PP2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.43	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.62		Gain of catalytic residue at S29 (P = 0);
MVP		0.58
MPC		2.3
ClinPred		0.99	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.58
gMVP		0.76

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: chr12-46123689;