1-22081613-G-A

Position:

• chr1-22081613-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001791.4(CDC42):​c.106-109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 685,394 control chromosomes in the GnomAD database, including 301,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68235 hom., cov: 32)
  • Exomes 𝑓: 0.93 (233222 hom.)
• Consequence: CDC42 NM_001791.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.981

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-22081613-G-A is Benign according to our data. Variant chr1-22081613-G-A is described in ClinVar as [Benign]. Clinvar id is 1283813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42	NM_001791.4	c.106-109G>A		intron_variant		ENST00000656825.1	NP_001782.1
CDC42	NM_001039802.2	c.106-109G>A		intron_variant			NP_001034891.1
CDC42	NM_044472.3	c.106-109G>A		intron_variant			NP_426359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42	ENST00000656825.1	c.106-109G>A		intron_variant			NM_001791.4	ENSP00000499457	P3

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143949 AN: 152178 Hom.: 68175 Cov.: 32

Gnomad AFR AF: 0.989

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.953

Gnomad ASJ AF: 0.930

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.925

Gnomad OTH AF: 0.955

GnomAD4 exome AF: 0.935 AC: 498442 AN: 533098 Hom.: 233222 AF XY: 0.934 AC XY: 268219 AN XY: 287156

Gnomad4 AFR exome AF: 0.988

Gnomad4 AMR exome AF: 0.965

Gnomad4 ASJ exome AF: 0.929

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.945

Gnomad4 FIN exome AF: 0.899

Gnomad4 NFE exome AF: 0.926

Gnomad4 OTH exome AF: 0.940

GnomAD4 genome AF: 0.946 AC: 144068 AN: 152296 Hom.: 68235 Cov.: 32 AF XY: 0.945 AC XY: 70395 AN XY: 74454

Gnomad4 AFR AF: 0.989

Gnomad4 AMR AF: 0.953

Gnomad4 ASJ AF: 0.930

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.946

Gnomad4 FIN AF: 0.889

Gnomad4 NFE AF: 0.925

Gnomad4 OTH AF: 0.955

Alfa AF: 0.931 Hom.: 8189

Bravo AF: 0.953

Asia WGS AF: 0.981 AC: 3411 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.7
DANN	Benign	0.62

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: rs2501282; hg19: chr1-22408106;