Variant 10-48446419-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021226.4(ARHGAP22):c.2069G>A(p.Gly690Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000563 in 1,614,118 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 3 hom. )

Consequence

ARHGAP22
NM_021226.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.35

Variant links:

Genes affected

ARHGAP22 (HGNC:30320): (Rho GTPase activating protein 22) This gene encodes a member of the GTPase activating protein family which activates a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues. The result of these interactions is regulation of cell motility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ARHGAP22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07255435).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP22	NM_021226.4 link	c.2069G>A	p.Gly690Glu	missense_variant	Exon 10 of 10	ENST00000249601.9	NP_067049.2	Q7Z5H3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP22	ENST00000249601.9 link	c.2069G>A	p.Gly690Glu	missense_variant	Exon 10 of 10	1	NM_021226.4	ENSP00000249601.4		Q7Z5H3-1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000402

AC:

101

AN:

251476

Hom.:

AF XY:

0.000478

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000527

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000594

AC:

869

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000615

AC XY:

447

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000904

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000670

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.000256

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000460

Hom.:

Bravo

AF:

0.000253

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000404

AC:

EpiCase

AF:

0.000709

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2069G>A (p.G690E) alteration is located in exon 10 (coding exon 10) of the ARHGAP22 gene. This alteration results from a G to A substitution at nucleotide position 2069, causing the glycine (G) at amino acid position 690 to be replaced by a glutamic acid (E). 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

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

T;T;T;.;.;.;.

Eigen

Benign

0.14

Eigen_PC

Benign

0.069

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

T;D;D;T;T;T;T

M_CAP

Benign

0.073

MetaRNN

Benign

0.073

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;.;.;.;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.4

N;N;D;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.040

D;T;D;D;D;T;D

Sift4G

Uncertain

0.034

D;D;T;T;T;D;D

Polyphen

1.0

D;D;.;.;D;.;D

Vest4

0.38

MVP

0.48

MPC

0.78

ClinPred

0.27

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over