Genetic Variant ARHGAP26:p.Asp729Asn (chr5-143214082-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

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

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

juvenile myelomonocytic leukemia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ARHGAP26 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3 link	c.2185G>A	p.Asp729Asn	missense_variant	Exon 22 of 23	ENST00000645722.2	NP_001129080.1	Q9UNA1-2A0A0S2Z536

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2 link	c.2185G>A	p.Asp729Asn	missense_variant	Exon 22 of 23		NM_001135608.3	ENSP00000495131.1		Q9UNA1-2
ARHGAP26	ENST00000425417.2 link	c.193G>A	p.Asp65Asn	missense_variant	Exon 2 of 3	5		ENSP00000403388.2		H7C205

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000959

AC:

AN:

208604

AF XY:

0.00

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 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

African (AFR)

AF:

0.000108

AC:

AN:

27678

American (AMR)

AF:

0.00

AC:

AN:

36990

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18806

East Asian (EAS)

AF:

0.00

AC:

AN:

23804

South Asian (SAS)

AF:

0.00

AC:

AN:

78888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35752

Middle Eastern (MID)

AF:

0.000636

AC:

AN:

4718

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

938040

Other (OTH)

AF:

0.00

AC:

AN:

46040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

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

(source)

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;.

PhyloP100

5.0

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

Mutation Taster

=64/36

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over