Variant chr2-143155632-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018460.4(ARHGAP15):c.142G>A(p.Asp48Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000127 in 1,578,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ARHGAP15
NM_018460.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.89

Variant links:

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]

ARHGAP15 links:

LOC107985949 (HGNC:):

LOC107985949 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.24005353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP15	NM_018460.4 linkuse as main transcript	c.142G>A	p.Asp48Asn	missense_variant	2/14	ENST00000295095.11
LOC107985949	XR_001739723.2 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ARHGAP15	ENST00000295095.11 linkuse as main transcript	c.142G>A	p.Asp48Asn	missense_variant	2/14	1	NM_018460.4	P1
ARHGAP15	ENST00000409869.5 linkuse as main transcript	c.142G>A	p.Asp48Asn	missense_variant	3/7	5
ARHGAP15	ENST00000552641.5 linkuse as main transcript	n.210G>A		non_coding_transcript_exon_variant	2/8	2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151742

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000275

AC:

AN:

217802

Hom.:

AF XY:

0.0000252

AC XY:

AN XY:

118818

show subpopulations

Gnomad AFR exome

AF:

0.0000688

Gnomad AMR exome

AF:

0.000123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000194

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000126

AC:

AN:

1427184

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

709296

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000263

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000100

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151742

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74078

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.142G>A (p.D48N) alteration is located in exon 2 (coding exon 1) of the ARHGAP15 gene. This alteration results from a G to A substitution at nucleotide position 142, causing the aspartic acid (D) at amino acid position 48 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.023

T;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

0.81

.;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.19

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.011

D;T

Polyphen

0.082

.;B

Vest4

0.36

MutPred

0.48

Gain of MoRF binding (P = 0.0301);Gain of MoRF binding (P = 0.0301);

MVP

0.55

MPC

0.15

ClinPred

0.56

GERP RS

6.1

Varity_R

0.23

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over