Variant chr22-37566377-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152243.3(CDC42EP1):c.28G>A(p.Ala10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,549,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

CDC42EP1
NM_152243.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

Variant links:

Genes affected

CDC42EP1 (HGNC:17014): (CDC42 effector protein 1) CDC42 is a member of the Rho GTPase family that regulates multiple cellular activities, including actin polymerization. The protein encoded by this gene is a CDC42 binding protein that mediates actin cytoskeleton reorganization at the plasma membrane. This protein is secreted and is primarily found in bone marrow. [provided by RefSeq, Jul 2008]

CDC42EP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03985372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42EP1	NM_152243.3 linkuse as main transcript	c.28G>A	p.Ala10Thr	missense_variant	2/3	ENST00000249014.5	NP_689449.1	Q00587-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDC42EP1	ENST00000249014.5 linkuse as main transcript	c.28G>A	p.Ala10Thr	missense_variant	2/3	1	NM_152243.3	ENSP00000249014.4	Q00587-1
CDC42EP1	ENST00000430687.1 linkuse as main transcript	c.28G>A	p.Ala10Thr	missense_variant	3/3	3		ENSP00000411682.1	B0QYC8
CDC42EP1	ENST00000415670.1 linkuse as main transcript	c.28G>A	p.Ala10Thr	missense_variant	2/2	3		ENSP00000405006.1	B0QYC7
CDC42EP1	ENST00000434728.1 linkuse as main transcript	c.28G>A	p.Ala10Thr	missense_variant	2/2	4		ENSP00000403710.1	B0QYC6

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000638

AC:

AN:

187944

Hom.:

AF XY:

0.0000393

AC XY:

AN XY:

101806

show subpopulations

Gnomad AFR exome

AF:

0.0000817

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000704

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000574

Gnomad NFE exome

AF:

0.000107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000169

AC:

236

AN:

1397620

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

116

AN XY:

688358

show subpopulations

Gnomad4 AFR exome

AF:

0.0000942

Gnomad4 AMR exome

AF:

0.0000270

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000271

Gnomad4 SAS exome

AF:

0.0000511

Gnomad4 FIN exome

AF:

0.0000199

Gnomad4 NFE exome

AF:

0.000203

Gnomad4 OTH exome

AF:

0.000122

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000976

Hom.:

Bravo

AF:

0.0000982

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000330

AC:

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

Dec 05, 2022

The c.28G>A (p.A10T) alteration is located in exon 2 (coding exon 1) of the CDC42EP1 gene. This alteration results from a G to A substitution at nucleotide position 28, causing the alanine (A) at amino acid position 10 to be replaced by a threonine (T). 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

0.086

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.025

T;T;T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.42

T;T;T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.040

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.57

N;N;N;N

REVEL

Benign

0.062

Sift

Benign

0.20

T;T;T;T

Sift4G

Benign

0.21

T;T;T;D

Polyphen

0.0010

B;.;.;.

Vest4

0.21

MutPred

0.14

Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);

MVP

0.32

MPC

0.057

ClinPred

0.0093

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.071

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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