12-45851241-G-C

Position:

• chr12-45851241-G-C

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.3118G>C​(p.Val1040Leu) 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. 13/21 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: 5.08

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=0.1646952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARID2	NM_152641.4	c.3118G>C	p.Val1040Leu	missense_variant	15/21	ENST00000334344.11	NP_689854.2
ARID2	NM_001347839.2	c.3118G>C	p.Val1040Leu	missense_variant	15/20		NP_001334768.1
ARID2	XM_047428489.1	c.3118G>C	p.Val1040Leu	missense_variant	15/17		XP_047284445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARID2	ENST00000334344.11	c.3118G>C	p.Val1040Leu	missense_variant	15/21	1	NM_152641.4	ENSP00000335044	P1
ARID2	ENST00000422737.7	c.3118G>C	p.Val1040Leu	missense_variant	15/20	1		ENSP00000415650
ARID2	ENST00000444670.5	c.1966G>C	p.Val656Leu	missense_variant	7/13	1		ENSP00000397307
ARID2	ENST00000479608.5	c.*1668G>C		3_prime_UTR_variant, NMD_transcript_variant	9/15	1		ENSP00000514783

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	0.16
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T;T;.
Eigen	Benign	-0.088
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D;.;D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;.;.
MutationTaster	Benign	0.80	D;D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.68	N;N;N
REVEL	Benign	0.070
Sift	Uncertain	0.014	D;D;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.037	B;.;B
Vest4		0.20
MutPred		0.33		Gain of catalytic residue at V1036 (P = 0.0057);.;.;
MVP		0.36
MPC		0.14
ClinPred		0.48	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr12-46245024;