1-22078812-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001791.4(CDC42):c.105+229C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000869 in 1,426,158 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (1 hom.)
• Consequence: CDC42 NM_001791.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.234

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 1-22078812-C-G is Benign according to our data. Variant chr1-22078812-C-G is described in ClinVar as [Benign]. Clinvar id is 1694499.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 155 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC42	NM_001791.4	c.105+229C>G		intron_variant		ENST00000656825.1
CDC42	NM_001039802.2	c.105+229C>G		intron_variant
CDC42	NM_044472.3	c.105+229C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC42	ENST00000656825.1	c.105+229C>G		intron_variant			NM_001791.4	P3

Frequencies

GnomAD3 genomes AF: 0.00102 AC: 155 AN: 151516 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000728

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000789

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00125

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00175

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000939 AC: 122 AN: 129976 Hom.: 1 AF XY: 0.000932 AC XY: 66 AN XY: 70832

Gnomad AFR exome AF: 0.000156

Gnomad AMR exome AF: 0.000454

Gnomad ASJ exome AF: 0.00234

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00220

Gnomad NFE exome AF: 0.00162

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000850 AC: 1084 AN: 1274642 Hom.: 1 Cov.: 31 AF XY: 0.000891 AC XY: 559 AN XY: 627508

Gnomad4 AFR exome AF: 0.000139

Gnomad4 AMR exome AF: 0.000373

Gnomad4 ASJ exome AF: 0.00236

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00171

Gnomad4 NFE exome AF: 0.000927

Gnomad4 OTH exome AF: 0.000824

GnomAD4 genome AF: 0.00102 AC: 155 AN: 151516 Hom.: 0 Cov.: 32 AF XY: 0.000920 AC XY: 68 AN XY: 73928

Gnomad4 AFR AF: 0.0000728

Gnomad4 AMR AF: 0.000789

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00125

Gnomad4 NFE AF: 0.00175

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00161 Hom.: 0

Bravo AF: 0.000718

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

CDC42: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	16
Dann	Benign	0.88

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

Other links and lift over

dbSNP: rs557013417; hg19: chr1-22405305; COSMIC: COSV100212759;