1-22081706-A-AT

Position:

• chr1-22081706-A-AT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001791.4(CDC42):​c.106-9dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00872 in 1,563,968 control chromosomes in the GnomAD database, including 69 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0089 (62 hom.)
• Consequence: CDC42 NM_001791.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.88

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-22081706-A-AT is Benign according to our data. Variant chr1-22081706-A-AT is described in ClinVar as [Benign]. Clinvar id is 1165494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 1103 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC42	NM_001791.4	c.106-9dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000656825.1
CDC42	NM_001039802.2	c.106-9dup		splice_polypyrimidine_tract_variant, intron_variant
CDC42	NM_044472.3	c.106-9dup		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC42	ENST00000656825.1	c.106-9dup		splice_polypyrimidine_tract_variant, intron_variant			NM_001791.4	P3

Frequencies

GnomAD3 genomes AF: 0.00725 AC: 1103 AN: 152082 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00143

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.00814

GnomAD3 exomes AF: 0.00741 AC: 1849 AN: 249480 Hom.: 14 AF XY: 0.00743 AC XY: 1002 AN XY: 134866

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00414

Gnomad ASJ exome AF: 0.00270

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00518

Gnomad FIN exome AF: 0.0122

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.00759

GnomAD4 exome AF: 0.00888 AC: 12534 AN: 1411768 Hom.: 62 Cov.: 25 AF XY: 0.00880 AC XY: 6205 AN XY: 705226

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.00486

Gnomad4 ASJ exome AF: 0.00283

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.00524

Gnomad4 FIN exome AF: 0.0125

Gnomad4 NFE exome AF: 0.00997

Gnomad4 OTH exome AF: 0.00754

GnomAD4 genome AF: 0.00725 AC: 1103 AN: 152200 Hom.: 7 Cov.: 33 AF XY: 0.00759 AC XY: 565 AN XY: 74434

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00634

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0160

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.0109 Hom.: 2

Bravo AF: 0.00630

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

CDC42-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 26, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: rs201214894; hg19: chr1-22408199;