rs2056974

Positions:

• chr1-22082601-T-A
• chr1-22082601-T-C
• chr1-22082601-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001791.4(CDC42):​c.178+807T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 152,148 control chromosomes in the GnomAD database, including 42,519 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (42519 hom., cov: 32)
• Consequence: CDC42 NM_001791.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=-0.46).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42	NM_001791.4	c.178+807T>A		intron_variant		ENST00000656825.1	NP_001782.1
CDC42	NM_001039802.2	c.178+807T>A		intron_variant			NP_001034891.1
CDC42	NM_044472.3	c.178+807T>A		intron_variant			NP_426359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42	ENST00000656825.1	c.178+807T>A		intron_variant			NM_001791.4	ENSP00000499457	P3

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113407 AN: 152030 Hom.: 42508 Cov.: 32

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.757

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.746 AC: 113455 AN: 152148 Hom.: 42519 Cov.: 32 AF XY: 0.748 AC XY: 55608 AN XY: 74388

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.876

Gnomad4 SAS AF: 0.882

Gnomad4 FIN AF: 0.732

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.760

Alfa AF: 0.746 Hom.: 5285

Bravo AF: 0.742

Asia WGS AF: 0.866 AC: 3006 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.92

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: rs2056974; hg19: chr1-22409094;