11-65321163-G-A

Variant summary

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

The NM_006779.4(CDC42EP2):​c.265G>A​(p.Ala89Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,613,930 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 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

CDC42EP2
NM_006779.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.103
Variant links:
Genes affected
CDC42EP2 (HGNC:16263): (CDC42 effector protein 2) CDC42, a small Rho GTPase, regulates the formation of F-actin-containing structures through its interaction with the downstream effector proteins. The protein encoded by this gene is a member of the Borg family of CDC42 effector proteins. Borg family proteins contain a CRIB (Cdc42/Rac interactive-binding) domain. They bind to, and negatively regulate the function of CDC42. Coexpression of this protein with CDC42 suggested a role of this protein in actin filament assembly and cell shape control. [provided by RefSeq, Aug 2011]

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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=0.029651761).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDC42EP2NM_006779.4 linkuse as main transcriptc.265G>A p.Ala89Thr missense_variant 2/2 ENST00000279249.3 NP_006770.1 O14613
CDC42EP2XM_047426244.1 linkuse as main transcriptc.265G>A p.Ala89Thr missense_variant 2/2 XP_047282200.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDC42EP2ENST00000279249.3 linkuse as main transcriptc.265G>A p.Ala89Thr missense_variant 2/21 NM_006779.4 ENSP00000279249.2 O14613
ENSG00000285816ENST00000649896.1 linkuse as main transcriptn.*591G>A non_coding_transcript_exon_variant 19/20 ENSP00000498025.1 A0A3B3ITS5
ENSG00000285816ENST00000649896.1 linkuse as main transcriptn.*591G>A 3_prime_UTR_variant 19/20 ENSP00000498025.1 A0A3B3ITS5
CDC42EP2ENST00000533419.1 linkuse as main transcriptc.265G>A p.Ala89Thr missense_variant 2/23 ENSP00000431660.1 O14613

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000524
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000677
AC:
17
AN:
251150
Hom.:
0
AF XY:
0.0000810
AC XY:
11
AN XY:
135784
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000120
AC:
176
AN:
1461804
Hom.:
0
Cov.:
32
AF XY:
0.000114
AC XY:
83
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000290
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000127
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152126
Hom.:
0
Cov.:
32
AF XY:
0.0000942
AC XY:
7
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.000524
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.000147
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsApr 07, 2022The c.265G>A (p.A89T) alteration is located in exon 2 (coding exon 1) of the CDC42EP2 gene. This alteration results from a G to A substitution at nucleotide position 265, causing the alanine (A) at amino acid position 89 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
0.083
BayesDel_addAF
Benign
-0.58
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
9.8
DANN
Benign
0.78
DEOGEN2
Benign
0.032
T;T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.56
.;T
M_CAP
Benign
0.0040
T
MetaRNN
Benign
0.030
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
M;M
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.48
N;N
REVEL
Benign
0.055
Sift
Benign
0.75
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0010
B;B
Vest4
0.022
MutPred
0.29
Gain of glycosylation at A89 (P = 0.0331);Gain of glycosylation at A89 (P = 0.0331);
MVP
0.30
ClinPred
0.021
T
GERP RS
3.3
Varity_R
0.016
gMVP
0.52

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.

Other links and lift over

dbSNP: rs201902468; hg19: chr11-65088634; API