Variant 2-68813372-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_001007231.3(ARHGAP25):c.760G>A(p.Glu254Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00559 in 1,613,670 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 20 hom. )

Consequence

ARHGAP25
NM_001007231.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.12

Variant links:

Genes affected

ARHGAP25 (HGNC:28951): (Rho GTPase activating protein 25) ARHGAPs, such as ARHGAP25, encode negative regulators of Rho GTPases (see ARHA; MIM 165390), which are implicated in actin remodeling, cell polarity, and cell migration (Katoh and Katoh, 2004 [PubMed 15254788]).[supplied by OMIM, Mar 2008]

ARHGAP25 links:

ARHGAP25 (HGNC:):

ARHGAP25 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 2-68813372-G-A is Benign according to our data. Variant chr2-68813372-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3357768.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP25	NM_001007231.3 linkuse as main transcript	c.760G>A	p.Glu254Lys	missense_variant	6/11	ENST00000409202.8	NP_001007232.2	P42331-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP25	ENST00000409202.8 linkuse as main transcript	c.760G>A	p.Glu254Lys	missense_variant	6/11	2	NM_001007231.3	ENSP00000386911.3		P42331-4

Frequencies

GnomAD3 genomes

AF:

0.00381

AC:

578

AN:

151832

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00335

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00161

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00654

Gnomad OTH

AF:

0.00289

GnomAD3 exomes

AF:

0.00350

AC:

879

AN:

251156

Hom.:

AF XY:

0.00345

AC XY:

468

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00227

Gnomad NFE exome

AF:

0.00643

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00578

AC:

8449

AN:

1461720

Hom.:

Cov.:

AF XY:

0.00558

AC XY:

4061

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.00247

Gnomad4 NFE exome

AF:

0.00706

Gnomad4 OTH exome

AF:

0.00556

GnomAD4 genome

AF:

0.00380

AC:

578

AN:

151950

Hom.:

Cov.:

AF XY:

0.00335

AC XY:

249

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00334

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00161

Gnomad4 NFE

AF:

0.00655

Gnomad4 OTH

AF:

0.00286

Alfa

AF:

0.00557

Hom.:

Bravo

AF:

0.00393

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00338

AC:

411

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00594

EpiControl

AF:

0.00599

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ARHGAP25-related condition

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 13, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Pathogenic

1.0

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;D;D;D;D

MetaRNN

Benign

0.0092

T;T;T;T;T

MetaSVM

Benign

-0.78

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.2

D;D;D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D;D

Polyphen

0.91

P;.;D;.;D

Vest4

0.50

MVP

0.47

MPC

0.38

ClinPred

0.018

GERP RS

5.7

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.21

Position offset: 47

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