rs2056974

Variant names:

• chr1-22082601-T-A
• rs2056974
• NM_001791.4:c.178+807T>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

CDC42 Gene-Disease associations (from GenCC):

• macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000289694 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001791.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42	NM_001791.4	MANE Select	c.178+807T>A		intron	N/A	NP_001782.1	P60953-2
	CDC42	NM_001039802.2		c.178+807T>A		intron	N/A	NP_001034891.1	P60953-2
	CDC42	NM_044472.3		c.178+807T>A		intron	N/A	NP_426359.1	P60953-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42	ENST00000656825.1	MANE Select	c.178+807T>A		intron	N/A	ENSP00000499457.1	P60953-2
	CDC42	ENST00000315554.15	TSL:1	c.178+807T>A		intron	N/A	ENSP00000314458.8	P60953-1
	CDC42	ENST00000344548.8	TSL:1	c.178+807T>A		intron	N/A	ENSP00000341072.3	P60953-2

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

African (AFR) AF: 0.687 AC: 28498 AN: 41504

American (AMR) AF: 0.741 AC: 11329 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2689 AN: 3472

East Asian (EAS) AF: 0.876 AC: 4533 AN: 5174

South Asian (SAS) AF: 0.882 AC: 4255 AN: 4822

European-Finnish (FIN) AF: 0.732 AC: 7737 AN: 10568

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 52035 AN: 67996

Other (OTH) AF: 0.760 AC: 1606 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.92
PhyloP100		1.2
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2056974; hg19: chr1-22409094;