5-142907803-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135608.3(ARHGAP26):c.932G>A(p.Gly311Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGAP26 NM_001135608.3 missense, splice_region
• Scores: Splicing: ADA: 0.01352
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19137585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP26	NM_001135608.3	c.932G>A	p.Gly311Glu	missense_variant, splice_region_variant	9/23	ENST00000645722.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.932G>A	p.Gly311Glu	missense_variant, splice_region_variant	9/23		NM_001135608.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.932G>A (p.G311E) alteration is located in exon 9 (coding exon 9) of the ARHGAP26 gene. This alteration results from a G to A substitution at nucleotide position 932, causing the glycine (G) at amino acid position 311 to be replaced by a glutamic acid (E). 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	0.23
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	22
Dann	Benign	0.97
DEOGEN2	Benign	0.22	T;.;T;.;.;.;.
Eigen	Benign	-0.15
Eigen_PC	Benign	0.087
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.19	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;L;.;.;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.21	N;.;N;.;.;N;.
REVEL	Benign	0.11
Sift	Benign	0.28	T;.;T;.;.;T;.
Sift4G	Benign	0.39	T;.;T;.;.;T;.
Polyphen		0.73	P;B;P;.;.;.;.
Vest4		0.37
MutPred		0.37		Gain of methylation at K306 (P = 0.1249);Gain of methylation at K306 (P = 0.1249);Gain of methylation at K306 (P = 0.1249);.;.;.;.;
MVP		0.38
MPC		1.6
ClinPred		0.75	D
GERP RS		5.8
Varity_R		0.12
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.014
dbscSNV1_RF	Benign	0.11
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-142287368;