Variant chr2-143155653-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018460.4(ARHGAP15):c.163C>A(p.Pro55Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000148 in 1,553,620 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ARHGAP15
NM_018460.4 missense, splice_region

Scores

Splicing: ADA: 0.9704

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP15	NM_018460.4 linkuse as main transcript	c.163C>A	p.Pro55Thr	missense_variant, splice_region_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.163C>A	p.Pro55Thr	missense_variant, splice_region_variant	2/14	1	NM_018460.4	P1
ARHGAP15	ENST00000409869.5 linkuse as main transcript	c.163C>A	p.Pro55Thr	missense_variant, splice_region_variant	3/7	5
ARHGAP15	ENST00000552641.5 linkuse as main transcript	n.231C>A		splice_region_variant, non_coding_transcript_exon_variant	2/8	2

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151714

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000250

AC:

AN:

200134

Hom.:

AF XY:

0.0000182

AC XY:

AN XY:

109644

show subpopulations

Gnomad AFR exome

AF:

0.000215

Gnomad AMR exome

AF:

0.00

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:

0.0000204

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1401906

Hom.:

Cov.:

AF XY:

0.0000158

AC XY:

AN XY:

695386

show subpopulations

Gnomad4 AFR exome

AF:

0.0000673

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:

0.0000165

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151714

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74062

show subpopulations

Gnomad4 AFR

AF:

0.0000726

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

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

Oct 12, 2022

The c.163C>A (p.P55T) alteration is located in exon 2 (coding exon 1) of the ARHGAP15 gene. This alteration results from a C to A substitution at nucleotide position 163, causing the proline (P) at amino acid position 55 to be replaced by a threonine (T). 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

0.10

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0090

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Benign

-1.2

MutationAssessor

Benign

0.63

.;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.17

Sift

Benign

0.040

D;T

Sift4G

Benign

0.14

T;T

Polyphen

0.56

.;P

Vest4

0.82

MVP

0.61

MPC

0.081

ClinPred

0.22

GERP RS

6.1

Varity_R

0.14

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Pathogenic

0.77

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

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