chr5-143214082-G-A

Variant names:

• chr5-143214082-G-A
• rs587778049
• NM_001135608.3:c.2185G>A
• ARHGAP26 p.Asp729Asn

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001135608.3(ARHGAP26):​c.2185G>A​(p.Asp729Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000182 in 1,210,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: ARHGAP26 NM_001135608.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 O:1
• Conservation: PhyloP100: 4.97
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23602396).

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.2185G>A	p.Asp729Asn	missense	Exon 22 of 23	NP_001129080.1	A0A0S2Z536
	ARHGAP26	NM_015071.6		c.2350G>A	p.Asp784Asn	missense	Exon 22 of 23	NP_055886.1	Q9UNA1-1
	ARHGAP26	NM_001349547.2		c.1966G>A	p.Asp656Asn	missense	Exon 21 of 22	NP_001336476.1	A0A2R8YGB3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP26	ENST00000645722.2	MANE Select	c.2185G>A	p.Asp729Asn	missense	Exon 22 of 23	ENSP00000495131.1	Q9UNA1-2
	ARHGAP26	ENST00000274498.9	TSL:1	c.2350G>A	p.Asp784Asn	missense	Exon 22 of 23	ENSP00000274498.4	Q9UNA1-1
	ARHGAP26	ENST00000418236.5	TSL:1	c.787G>A	p.Asp263Asn	missense	Exon 7 of 8	ENSP00000416889.1	H0Y835

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000959 AC: 2 AN: 208604 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000226

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000182 AC: 22 AN: 1210716 Hom.: 0 Cov.: 26 AF XY: 0.0000217 AC XY: 13 AN XY: 598024

African (AFR) AF: 0.000108 AC: 3 AN: 27678

American (AMR) AF: 0.00 AC: 0 AN: 36990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18806

East Asian (EAS) AF: 0.00 AC: 0 AN: 23804

South Asian (SAS) AF: 0.00 AC: 0 AN: 78888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35752

Middle Eastern (MID) AF: 0.000636 AC: 3 AN: 4718

European-Non Finnish (NFE) AF: 0.0000171 AC: 16 AN: 938040

Other (OTH) AF: 0.00 AC: 0 AN: 46040

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000302 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.55
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.51	N
PhyloP100		5.0
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.084
Sift	Benign	0.15	T
Sift4G	Benign	0.46	T
Varity_R		0.080
gMVP		0.69
Mutation Taster		=64/36	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

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

Other links and lift over

dbSNP: rs587778049;

hg19: chr5-142593647;