2-143250520-C-A

Variant names:

• chr2-143250520-C-A
• NM_018460.4:c.394C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018460.4(ARHGAP15):​c.394C>A​(p.His132Asn) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGAP15 NM_018460.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0300
• Publications: 0 publications found

Genes affected

ARHGAP15 (HGNC:21030): (Rho GTPase activating protein 15) RHO GTPases (see ARHA; MIM 165390) regulate diverse biologic processes, and their activity is regulated by RHO GTPase-activating proteins (GAPs), such as ARHGAP15 (Seoh et al., 2003 [PubMed 12650940]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.068479925).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018460.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP15	NM_018460.4	MANE Select	c.394C>A	p.His132Asn	missense	Exon 6 of 14	NP_060930.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP15	ENST00000295095.11	TSL:1 MANE Select	c.394C>A	p.His132Asn	missense	Exon 6 of 14	ENSP00000295095.6	Q53QZ3
	ARHGAP15	ENST00000906468.1		c.394C>A	p.His132Asn	missense	Exon 6 of 15	ENSP00000576527.1
	ARHGAP15	ENST00000906471.1		c.394C>A	p.His132Asn	missense	Exon 6 of 14	ENSP00000576530.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.5
DANN	Benign	0.84
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.090	N
PhyloP100		-0.030
PrimateAI	Benign	0.39	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.14
Sift	Benign	0.29	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.46		Gain of catalytic residue at H132 (P = 0.0428)
MVP		0.64
MPC		0.060
ClinPred		0.028	T
GERP RS		-0.41
Varity_R		0.032
gMVP		0.084
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

hg19: chr2-144008089;