1-22078709-T-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001791.4(CDC42):c.105+126T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,509,282 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (14 hom., cov: 32)
  • Exomes 𝑓: 0.011 (88 hom.)
• Consequence: CDC42 NM_001791.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.22

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 1-22078709-T-A is Benign according to our data. Variant chr1-22078709-T-A is described in ClinVar as [Benign]. Clinvar id is 1694498.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 1175 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC42	NM_001791.4	c.105+126T>A		intron_variant		ENST00000656825.1
CDC42	NM_001039802.2	c.105+126T>A		intron_variant
CDC42	NM_044472.3	c.105+126T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC42	ENST00000656825.1	c.105+126T>A		intron_variant			NM_001791.4	P3

Frequencies

GnomAD3 genomes AF: 0.00772 AC: 1175 AN: 152192 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00698 AC: 942 AN: 135030 Hom.: 7 AF XY: 0.00675 AC XY: 488 AN XY: 72286

Gnomad AFR exome AF: 0.00170

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.00239

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000822

Gnomad FIN exome AF: 0.0181

Gnomad NFE exome AF: 0.0115

Gnomad OTH exome AF: 0.00487

GnomAD4 exome AF: 0.0110 AC: 14928 AN: 1356972 Hom.: 88 Cov.: 30 AF XY: 0.0105 AC XY: 7053 AN XY: 668776

Gnomad4 AFR exome AF: 0.00160

Gnomad4 AMR exome AF: 0.00196

Gnomad4 ASJ exome AF: 0.00185

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000796

Gnomad4 FIN exome AF: 0.0173

Gnomad4 NFE exome AF: 0.0128

Gnomad4 OTH exome AF: 0.00815

GnomAD4 genome AF: 0.00771 AC: 1174 AN: 152310 Hom.: 14 Cov.: 32 AF XY: 0.00777 AC XY: 579 AN XY: 74474

Gnomad4 AFR AF: 0.00195

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0193

Gnomad4 NFE AF: 0.0123

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00954 Hom.: 5

Bravo AF: 0.00605

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

Jul 01, 2023

CDC42: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
Cadd	Benign	18
Dann	Uncertain	0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs75284716; hg19: chr1-22405202; COSMIC: COSV104537548;