rs587778050

Positions:

• chr5-142875166-C-T

Variant summary

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

The NM_001135608.3(ARHGAP26):​c.307C>T​(p.Arg103Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ARHGAP26 NM_001135608.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 3.05

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3	c.307C>T	p.Arg103Trp	missense_variant	3/23	ENST00000645722.2	NP_001129080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.307C>T	p.Arg103Trp	missense_variant	3/23		NM_001135608.3	ENSP00000495131	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461782 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727206

Gnomad4 AFR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;.;T;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.99	.;D;D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.48	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.3	M;M;M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-4.3	D;.;D;.;.
REVEL	Benign	0.28
Sift	Uncertain	0.020	D;.;D;.;.
Sift4G	Uncertain	0.027	D;.;T;.;.
Polyphen		1.0	D;D;D;.;.
Vest4		0.70
MutPred		0.49		Loss of disorder (P = 0.012);Loss of disorder (P = 0.012);Loss of disorder (P = 0.012);.;.;
MVP		0.55
MPC		1.4
ClinPred		0.99	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.62

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

Other links and lift over

dbSNP: rs587778050; hg19: chr5-142254731;