rs16826534

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001791.4(CDC42):c.276C>T(p.Asn92Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,607,852 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00089 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 5 hom. )

Consequence

CDC42
NM_001791.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.41

Publications

2 publications found

Variant links:

Genes affected

CDC42 (HGNC:1736): (cell division cycle 42) The protein encoded by this gene is a small GTPase of the Rho-subfamily, which regulates signaling pathways that control diverse cellular functions including cell morphology, migration, endocytosis and cell cycle progression. This protein is highly similar to Saccharomyces cerevisiae Cdc 42, and is able to complement the yeast cdc42-1 mutant. The product of oncogene Dbl was reported to specifically catalyze the dissociation of GDP from this protein. This protein could regulate actin polymerization through its direct binding to Neural Wiskott-Aldrich syndrome protein (N-WASP), which subsequently activates Arp2/3 complex. Alternative splicing of this gene results in multiple transcript variants. Pseudogenes of this gene have been identified on chromosomes 3, 4, 5, 7, 8 and 20. [provided by RefSeq, Apr 2013]

CDC42 Gene-Disease associations (from GenCC):

macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

CDC42 links:

ENSG00000289694 (HGNC:):

ENSG00000289694 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 1-22086536-C-T is Benign according to our data. Variant chr1-22086536-C-T is described in ClinVar as Benign. ClinVar VariationId is 730778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.41 with no splicing effect.

BS2

High AC in GnomAd4 at 135 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC42	NM_001791.4 link	c.276C>T	p.Asn92Asn	synonymous_variant	Exon 4 of 6	ENST00000656825.1	NP_001782.1	P60953-2A0A024RAA5
CDC42	NM_001039802.2 link	c.276C>T	p.Asn92Asn	synonymous_variant	Exon 5 of 7		NP_001034891.1	P60953-2A0A024RAA5
CDC42	NM_044472.3 link	c.276C>T	p.Asn92Asn	synonymous_variant	Exon 4 of 6		NP_426359.1	P60953-1A0A024RAA6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42	ENST00000656825.1 link	c.276C>T	p.Asn92Asn	synonymous_variant	Exon 4 of 6		NM_001791.4	ENSP00000499457.1		P60953-2
ENSG00000289694	ENST00000695856.1 link	c.276C>T	p.Asn92Asn	synonymous_variant	Exon 4 of 6			ENSP00000512221.1

Frequencies

GnomAD3 genomes

AF:

0.000875

AC:

133

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000983

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00121

AC:

301

AN:

249510

AF XY:

0.00121

show subpopulations

Gnomad AFR exome

AF:

0.000630

Gnomad AMR exome

AF:

0.000847

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00289

Gnomad FIN exome

AF:

0.0000926

Gnomad NFE exome

AF:

0.00148

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00147

AC:

2143

AN:

1455648

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

1071

AN XY:

723608

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

33310

American (AMR)

AF:

0.00112

AC:

AN:

44464

Ashkenazi Jewish (ASJ)

AF:

0.000269

AC:

AN:

26070

East Asian (EAS)

AF:

0.00276

AC:

109

AN:

39556

South Asian (SAS)

AF:

0.000757

AC:

AN:

85834

European-Finnish (FIN)

AF:

0.000112

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00157

AC:

1741

AN:

1107138

Other (OTH)

AF:

0.00180

AC:

108

AN:

60136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

172

258

344

430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000887

AC:

135

AN:

152204

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.000506

AC:

AN:

41540

American (AMR)

AF:

0.000982

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00328

AC:

AN:

5186

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00107

AC:

AN:

67992

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00143

Hom.:

Bravo

AF:

0.000941

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00169

EpiControl

AF:

0.00119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CDC42: BS1, BS2 -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Mutation Taster

=96/4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over