chr1-22084526-T-G

Variant names:

• chr1-22084526-T-G
• rs2473316
• NM_001791.4:c.179-1913T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001791.4(CDC42):​c.179-1913T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 150,804 control chromosomes in the GnomAD database, including 44,236 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 0.77 (44236 hom., cov: 26)
• Consequence: CDC42 NM_001791.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.938
• 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: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000289694 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.859 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42	NM_001791.4	MANE Select	c.179-1913T>G		intron	N/A	NP_001782.1
	CDC42	NM_001039802.2		c.179-1913T>G		intron	N/A	NP_001034891.1
	CDC42	NM_044472.3		c.179-1913T>G		intron	N/A	NP_426359.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42	ENST00000656825.1	MANE Select	c.179-1913T>G		intron	N/A	ENSP00000499457.1
	CDC42	ENST00000315554.15	TSL:1	c.179-1913T>G		intron	N/A	ENSP00000314458.8
	CDC42	ENST00000344548.8	TSL:1	c.179-1913T>G		intron	N/A	ENSP00000341072.3

Frequencies

GnomAD3 genomes AF: 0.765 AC: 115330 AN: 150686 Hom.: 44216 Cov.: 26

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.765 AC: 115389 AN: 150804 Hom.: 44236 Cov.: 26 AF XY: 0.766 AC XY: 56416 AN XY: 73642

African (AFR) AF: 0.757 AC: 31081 AN: 41034

American (AMR) AF: 0.747 AC: 11321 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2612 AN: 3462

East Asian (EAS) AF: 0.878 AC: 4494 AN: 5118

South Asian (SAS) AF: 0.881 AC: 4198 AN: 4764

European-Finnish (FIN) AF: 0.729 AC: 7482 AN: 10266

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 51841 AN: 67716

Other (OTH) AF: 0.767 AC: 1599 AN: 2084

Alfa AF: 0.681 Hom.: 1970

Bravo AF: 0.765

Asia WGS AF: 0.869 AC: 3013 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.56
DANN	Benign	0.34
PhyloP100		-0.94
Mutation Taster		=100/0	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: rs2473316; hg19: chr1-22411019;