Genetic Variant CDC42BPA:p.Ala1734Asp (chr1-226994332-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001387550.1(CDC42BPA):c.5474C>A(p.Ala1825Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CDC42BPA
NM_001387550.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.04

Publications

26 publications found

Variant links:

Genes affected

CDC42BPA (HGNC:1737): (CDC42 binding protein kinase alpha) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase contains multiple functional domains. Its kinase domain is highly similar to that of the myotonic dystrophy protein kinase (DMPK). This kinase also contains a Rac interactive binding (CRIB) domain, and has been shown to bind CDC42. It may function as a CDC42 downstream effector mediating CDC42 induced peripheral actin formation, and promoting cytoskeletal reorganization. Multiple alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2018]

CDC42BPA links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05935514).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387550.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CDC42BPA	NM_001394014.1	MANE Select	c.5201C>A	p.Ala1734Asp	missense	Exon 37 of 37	NP_001380943.1
CDC42BPA	NM_001387550.1		c.5474C>A	p.Ala1825Asp	missense	Exon 40 of 40	NP_001374479.1
CDC42BPA	NM_001366019.2		c.5135C>A	p.Ala1712Asp	missense	Exon 37 of 37	NP_001352948.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CDC42BPA	ENST00000366766.8	TSL:5 MANE Select	c.5201C>A	p.Ala1734Asp	missense	Exon 37 of 37	ENSP00000355728.5
CDC42BPA	ENST00000366769.7	TSL:1	c.5096C>A	p.Ala1699Asp	missense	Exon 36 of 36	ENSP00000355731.3
CDC42BPA	ENST00000366764.8	TSL:1	c.5036C>A	p.Ala1679Asp	missense	Exon 36 of 36	ENSP00000355726.5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1445836

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717670

African (AFR)

AF:

0.00

AC:

AN:

33206

American (AMR)

AF:

0.00

AC:

AN:

43048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25678

East Asian (EAS)

AF:

0.00

AC:

AN:

39302

South Asian (SAS)

AF:

0.00

AC:

AN:

83846

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102948

Other (OTH)

AF:

0.00

AC:

AN:

59684

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.064

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.80

M_CAP

Benign

0.042

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

PhyloP100

2.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.26

REVEL

Benign

0.15

Sift

Uncertain

0.0080

Sift4G

Benign

0.58

Polyphen

0.37

Vest4

0.11

MutPred

0.12

Loss of glycosylation at P1681 (P = 0.0885)

MVP

0.43

MPC

0.50

ClinPred

0.18

GERP RS

1.2

Varity_R

0.14

gMVP

0.39

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over