rs587778048

Variant names:

• chr5-143134043-A-G
• rs587778048
• NM_001135608.3:c.1775A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135608.3(ARHGAP26):​c.1775A>G​(p.Lys592Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: ARHGAP26 NM_001135608.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 6.50
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24845222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3	c.1775A>G	p.Lys592Arg	missense_variant	Exon 19 of 23	ENST00000645722.2	NP_001129080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.1775A>G	p.Lys592Arg	missense_variant	Exon 19 of 23		NM_001135608.3	ENSP00000495131.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.;T;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	.;D;D;D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.1	M;M;M;.
PhyloP100		6.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.87	N;.;N;.
REVEL	Benign	0.17
Sift	Benign	0.12	T;.;T;.
Sift4G	Benign	0.53	T;.;T;.
Polyphen		0.99	D;D;D;.
Vest4		0.41
MutPred		0.32		Loss of solvent accessibility (P = 0.0083);Loss of solvent accessibility (P = 0.0083);Loss of solvent accessibility (P = 0.0083);.;
MVP		0.65
MPC		0.63
ClinPred		0.69	D
GERP RS		6.0
Varity_R		0.13
gMVP		0.42
Mutation Taster		=85/15	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: rs587778048; hg19: chr5-142513608;