Variant chr5-142770884-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001135608.3(ARHGAP26):c.123G>C(p.Lys41Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,928 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: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ARHGAP26
NM_001135608.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20609966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3 link	c.123G>C	p.Lys41Asn	missense_variant	1/23	ENST00000645722.2	NP_001129080.1	Q9UNA1-2A0A0S2Z536

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2 link	c.123G>C	p.Lys41Asn	missense_variant	1/23		NM_001135608.3	ENSP00000495131.1		Q9UNA1-2
ARHGAP26	ENST00000274498.9 link	c.123G>C	p.Lys41Asn	missense_variant	1/23	1		ENSP00000274498.4		Q9UNA1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458928

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725892

show subpopulations

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.123G>C (p.K41N) alteration is located in exon 1 (coding exon 1) of the ARHGAP26 gene. This alteration results from a G to C substitution at nucleotide position 123, causing the lysine (K) at amino acid position 41 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;.;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.97

.;D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

M;M;M

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.7

D;.;D

REVEL

Benign

0.14

Sift

Uncertain

0.0010

D;.;T

Sift4G

Uncertain

0.057

T;.;T

Polyphen

1.0

D;B;D

Vest4

0.63

MutPred

0.32

Gain of ubiquitination at K44 (P = 0.0291);Gain of ubiquitination at K44 (P = 0.0291);Gain of ubiquitination at K44 (P = 0.0291);

MVP

0.69

MPC

1.3

ClinPred

0.99

GERP RS

3.9

Varity_R

0.83

gMVP

0.72

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over