5-142770804-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001135608.3(ARHGAP26):​c.43A>G​(p.Ser15Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,448,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ARHGAP26
NM_001135608.3 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.16

Publications

0 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.813

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGAP26NM_001135608.3 linkc.43A>G p.Ser15Gly missense_variant Exon 1 of 23 ENST00000645722.2 NP_001129080.1 Q9UNA1-2A0A0S2Z536

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGAP26ENST00000645722.2 linkc.43A>G p.Ser15Gly missense_variant Exon 1 of 23 NM_001135608.3 ENSP00000495131.1 Q9UNA1-2
ARHGAP26ENST00000274498.9 linkc.43A>G p.Ser15Gly missense_variant Exon 1 of 23 1 ENSP00000274498.4 Q9UNA1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.90e-7
AC:
1
AN:
1448262
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
720716
show subpopulations
African (AFR)
AF:
0.0000311
AC:
1
AN:
32184
American (AMR)
AF:
0.00
AC:
0
AN:
43600
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25762
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37772
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85172
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52956
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5702
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1105376
Other (OTH)
AF:
0.00
AC:
0
AN:
59738
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 15, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.43A>G (p.S15G) alteration is located in exon 1 (coding exon 1) of the ARHGAP26 gene. This alteration results from a A to G substitution at nucleotide position 43, causing the serine (S) at amino acid position 15 to be replaced by a glycine (G). 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
Pathogenic
0.59
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
30
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
T;.;T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
.;D;D
M_CAP
Uncertain
0.19
D
MetaRNN
Pathogenic
0.81
D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.0
M;M;M
PhyloP100
7.2
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-3.1
D;.;D
REVEL
Uncertain
0.43
Sift
Pathogenic
0.0
D;.;D
Sift4G
Pathogenic
0.0
D;.;D
Polyphen
1.0
D;D;D
Vest4
0.68
MutPred
0.61
Loss of disorder (P = 0.0637);Loss of disorder (P = 0.0637);Loss of disorder (P = 0.0637);
MVP
0.60
MPC
0.58
ClinPred
0.99
D
GERP RS
4.4
PromoterAI
-0.067
Neutral
Varity_R
0.81
gMVP
0.80
Mutation Taster
=61/39
polymorphism

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

Other links and lift over

hg19: chr5-142150369; API