rs975495910

Variant names:

• chr5-142873418-G-A
• rs975495910
• NM_001135608.3:c.173G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-142873418-G-A
• chr5-142873418-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001135608.3(ARHGAP26):​c.173G>A​(p.Arg58Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000764 in 1,440,696 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R58L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: ARHGAP26 NM_001135608.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.11
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36597353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3	c.173G>A	p.Arg58Gln	missense_variant	Exon 2 of 23	ENST00000645722.2	NP_001129080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.173G>A	p.Arg58Gln	missense_variant	Exon 2 of 23		NM_001135608.3	ENSP00000495131.1
ARHGAP26	ENST00000274498.9	c.173G>A	p.Arg58Gln	missense_variant	Exon 2 of 23	1		ENSP00000274498.4
ARHGAP26	ENST00000642734.1	c.65G>A	p.Arg22Gln	missense_variant	Exon 2 of 22			ENSP00000495827.1
ARHGAP26	ENST00000378013.2	n.153G>A		non_coding_transcript_exon_variant	Exon 2 of 6	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000433 AC: 1 AN: 230698 AF XY: 0.00000799

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: 0.00000921

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000764 AC: 11 AN: 1440696 Hom.: 0 Cov.: 30 AF XY: 0.00000837 AC XY: 6 AN XY: 716430

African (AFR) AF: 0.00 AC: 0 AN: 32108

American (AMR) AF: 0.0000264 AC: 1 AN: 37846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25368

East Asian (EAS) AF: 0.00 AC: 0 AN: 39312

South Asian (SAS) AF: 0.00 AC: 0 AN: 81402

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000723 AC: 8 AN: 1106432

Other (OTH) AF: 0.0000168 AC: 1 AN: 59684

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.173G>A (p.R58Q) alteration is located in exon 2 (coding exon 2) of the ARHGAP26 gene. This alteration results from a G to A substitution at nucleotide position 173, causing the arginine (R) at amino acid position 58 to be replaced by a glutamine (Q). 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	0.14
BayesDel_addAF	Benign	0.0096	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	T;.;T;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L;L;.
PhyloP100		7.1
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.3	N;.;N;.
REVEL	Uncertain	0.30
Sift	Benign	0.43	T;.;T;.
Sift4G	Benign	0.46	T;.;T;.
Polyphen		1.0	D;D;D;.
Vest4		0.37
MutPred		0.30		Loss of MoRF binding (P = 0.0208);Loss of MoRF binding (P = 0.0208);Loss of MoRF binding (P = 0.0208);.;
MVP		0.71
MPC		0.60
ClinPred		0.83	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.22
gMVP		0.68
Mutation Taster		=73/27	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

Other links and lift over

dbSNP: rs975495910; hg19: chr5-142252983;