5-143214082-GAT-AAC

Variant names:

• chr5-143214082-GAT-AAC
• NM_001135608.3:c.2185_2187delGATinsAAC
• ARHGAP26 p.Asp729Asn

Variant summary

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

The NM_001135608.3(ARHGAP26):​c.2185_2187delGATinsAAC​(p.Asp729Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ARHGAP26 NM_001135608.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.33
• 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 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135608.3. 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.2185_2187delGATinsAAC	p.Asp729Asn	missense	N/A	NP_001129080.1	A0A0S2Z536
	ARHGAP26	NM_015071.6		c.2350_2352delGATinsAAC	p.Asp784Asn	missense	N/A	NP_055886.1	Q9UNA1-1
	ARHGAP26	NM_001349547.2		c.1966_1968delGATinsAAC	p.Asp656Asn	missense	N/A	NP_001336476.1	A0A2R8YGB3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP26	ENST00000645722.2	MANE Select	c.2185_2187delGATinsAAC	p.Asp729Asn	missense	N/A	ENSP00000495131.1	Q9UNA1-2
	ARHGAP26	ENST00000274498.9	TSL:1	c.2350_2352delGATinsAAC	p.Asp784Asn	missense	N/A	ENSP00000274498.4	Q9UNA1-1
	ARHGAP26	ENST00000418236.5	TSL:1	c.787_789delGATinsAAC	p.Asp263Asn	missense	N/A	ENSP00000416889.1	H0Y835

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-142593647;