dbSNP rs545978830: CDC42BPA:p.Ser1735Ala (chr1-226994330-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001394014.1(CDC42BPA):c.5203T>G(p.Ser1735Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,796 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1735T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CDC42BPA
NM_001394014.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.59

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394014.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDC42BPA	NM_001394014.1	MANE Select	c.5203T>G	p.Ser1735Ala	missense	Exon 37 of 37	NP_001380943.1	Q5VT25-2
CDC42BPA	NM_001387550.1		c.5476T>G	p.Ser1826Ala	missense	Exon 40 of 40	NP_001374479.1	A0A0A0MRJ1
CDC42BPA	NM_001366019.2		c.5137T>G	p.Ser1713Ala	missense	Exon 37 of 37	NP_001352948.1	Q5VT25-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDC42BPA	ENST00000366766.8	TSL:5 MANE Select	c.5203T>G	p.Ser1735Ala	missense	Exon 37 of 37	ENSP00000355728.5	Q5VT25-2
CDC42BPA	ENST00000366769.7	TSL:1	c.5098T>G	p.Ser1700Ala	missense	Exon 36 of 36	ENSP00000355731.3	Q5VT25-5
CDC42BPA	ENST00000366764.8	TSL:1	c.5038T>G	p.Ser1680Ala	missense	Exon 36 of 36	ENSP00000355726.5	A0A0A0MRJ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1447796

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718796

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33252

American (AMR)

AF:

0.00

AC:

AN:

43322

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25696

East Asian (EAS)

AF:

0.00

AC:

AN:

39374

South Asian (SAS)

AF:

0.00

AC:

AN:

84006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1104118

Other (OTH)

AF:

0.00

AC:

AN:

59820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.089

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.073

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.54

MetaSVM

Uncertain

0.00040

MutationAssessor

Benign

2.0

PhyloP100

8.6

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.30

Sift

Benign

0.13

Sift4G

Benign

0.26

Polyphen

0.93

Vest4

0.39

MutPred

0.15

Loss of phosphorylation at S1680 (P = 8e-04)

MVP

0.64

MPC

0.78

ClinPred

0.94

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.26

gMVP

0.35

Mutation Taster

=84/16

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