Variant rs587778049 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001135608.3(ARHGAP26):c.2185G>A(p.Asp729Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000182 in 1,210,716 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 not provided (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ARHGAP26
NM_001135608.3 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 4.97

Variant links:

Genes affected

ARHGAP26 (HGNC:17073): (Rho GTPase activating protein 26) Interaction of a cell with the extracellular matrix triggers integrin cell surface receptors to begin signaling cascades that regulate the organization of the actin-cytoskeleton. One of the proteins involved in these cascades is focal adhesion kinase. The protein encoded by this gene is a GTPase activating protein that binds to focal adhesion kinase and mediates the activity of the GTP binding proteins RhoA and Cdc42. Defects in this gene are a cause of juvenile myelomonocytic leukemia (JMML). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2017]

ARHGAP26 links:

ARHGAP26 (HGNC:):

ARHGAP26 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23602396).

BS2

High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3 linkuse as main transcript	c.2185G>A	p.Asp729Asn	missense_variant	22/23	ENST00000645722.2	NP_001129080.1	Q9UNA1-2A0A0S2Z536

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2 linkuse as main transcript	c.2185G>A	p.Asp729Asn	missense_variant	22/23		NM_001135608.3	ENSP00000495131.1		Q9UNA1-2
ARHGAP26	ENST00000425417.2 linkuse as main transcript	c.193G>A	p.Asp65Asn	missense_variant	2/3	5		ENSP00000403388.2		H7C205

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000959

AC:

AN:

208604

Hom.:

AF XY:

0.00

AC XY:

AN XY:

111386

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000226

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000182

AC:

AN:

1210716

Hom.:

Cov.:

AF XY:

0.0000217

AC XY:

AN XY:

598024

show subpopulations

Gnomad4 AFR exome

AF:

0.000108

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:

0.0000171

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000302

Hom.:

ExAC

AF:

0.00000836

AC:

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.55

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

T;.;T;.

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.76

.;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.24

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.51

N;.;N;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.67

N;.;.;.

REVEL

Benign

0.084

Sift

Benign

0.15

T;.;.;.

Sift4G

Benign

0.46

T;.;.;.

Polyphen

0.51

P;P;P;.

Vest4

0.14

MutPred

0.39

Loss of catalytic residue at D784 (P = 0.0555);.;Loss of catalytic residue at D784 (P = 0.0555);.;

MVP

0.64

MPC

0.56

ClinPred

0.29

GERP RS

5.2

Varity_R

0.080

gMVP

0.69

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

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