rs200775326

Variant names:

• chr12-45730131-C-A
• NM_152641.4:c.180C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-45730131-C-A
• chr12-45730131-C-G
• chr12-45730131-C-T

Variant summary

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

The NM_152641.4(ARID2):​c.180C>A​(p.Phe60Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F60F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ARID2 NM_152641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.814

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARID2	NM_152641.4	c.180C>A	p.Phe60Leu	missense_variant	Exon 2 of 21	ENST00000334344.11	NP_689854.2
ARID2	NM_001347839.2	c.180C>A	p.Phe60Leu	missense_variant	Exon 2 of 20		NP_001334768.1
ARID2	XM_047428489.1	c.180C>A	p.Phe60Leu	missense_variant	Exon 2 of 17		XP_047284445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARID2	ENST00000334344.11	c.180C>A	p.Phe60Leu	missense_variant	Exon 2 of 21	1	NM_152641.4	ENSP00000335044.6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.048
Eigen_PC	Benign	-0.040
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.62	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.2	L
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.38
Sift	Benign	0.13	T
Sift4G	Uncertain	0.044	D
Polyphen		0.99	D
Vest4		0.37
MutPred		0.76		Gain of catalytic residue at T56 (P = 0.0176);
MVP		0.47
MPC		1.2
ClinPred		0.78	D
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.19
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: chr12-46123914;