rs587778047

Variant names:

• chr5-143041850-T-GTGGGG
• rs587778047
• NM_001135608.3:c.1245delTinsGTGGGG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP7

The NM_015071.6(ARHGAP26):​c.1245delTinsGTGGGG​(p.Val416TrpfsTer11) variant causes a frameshift, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars). Synonymous variant affecting the same amino acid position (i.e. G415G) has been classified as Benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ARHGAP26 NM_015071.6 frameshift, synonymous
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.02
• 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
• BP7: Synonymous conserved (PhyloP=1.02 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015071.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP26	NM_001135608.3	MANE Select	c.1245delTinsGTGGGG	p.Val416TrpfsTer11	frameshift synonymous	Exon 14 of 23	NP_001129080.1
	ARHGAP26	NM_015071.6		c.1245delTinsGTGGGG	p.Val416TrpfsTer11	frameshift synonymous	Exon 14 of 23	NP_055886.1
	ARHGAP26	NM_001349547.2		c.1137delTinsGTGGGG	p.Val380TrpfsTer11	frameshift synonymous	Exon 14 of 22	NP_001336476.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP26	ENST00000645722.2	MANE Select	c.1245delTinsGTGGGG	p.Val416TrpfsTer11	frameshift synonymous	Exon 14 of 23	ENSP00000495131.1
	ARHGAP26	ENST00000274498.9	TSL:1	c.1245delTinsGTGGGG	p.Val416TrpfsTer11	frameshift synonymous	Exon 14 of 23	ENSP00000274498.4
	ARHGAP26	ENST00000642734.1		c.1137delTinsGTGGGG	p.Val380TrpfsTer11	frameshift synonymous	Exon 14 of 22	ENSP00000495827.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions as Germline

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587778047; hg19: chr5-142421415;