1-22078812-C-G

Variant names:

• chr1-22078812-C-G
• rs557013417
• NM_001791.4:c.105+229C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001791.4(CDC42):​c.105+229C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000869 in 1,426,158 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (1 hom.)
• Consequence: CDC42 NM_001791.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.234
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.106).
• BP6: Variant 1-22078812-C-G is Benign according to our data. Variant chr1-22078812-C-G is described in ClinVar as Benign. ClinVar VariationId is 1694499.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 155 AD gene.

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.105+229C>G		intron	N/A	NP_001782.1	P60953-2
	CDC42	NM_001039802.2		c.105+229C>G		intron	N/A	NP_001034891.1	P60953-2
	CDC42	NM_044472.3		c.105+229C>G		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.105+229C>G		intron	N/A	ENSP00000499457.1	P60953-2
	CDC42	ENST00000315554.15	TSL:1	c.105+229C>G		intron	N/A	ENSP00000314458.8	P60953-1
	CDC42	ENST00000344548.8	TSL:1	c.105+229C>G		intron	N/A	ENSP00000341072.3	P60953-2

Frequencies

GnomAD3 genomes AF: 0.00102 AC: 155 AN: 151516 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000728

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000789

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00125

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00175

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000939 AC: 122 AN: 129976 AF XY: 0.000932

Gnomad AFR exome AF: 0.000156

Gnomad AMR exome AF: 0.000454

Gnomad ASJ exome AF: 0.00234

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00220

Gnomad NFE exome AF: 0.00162

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000850 AC: 1084 AN: 1274642 Hom.: 1 Cov.: 31 AF XY: 0.000891 AC XY: 559 AN XY: 627508

African (AFR) AF: 0.000139 AC: 4 AN: 28864

American (AMR) AF: 0.000373 AC: 12 AN: 32192

Ashkenazi Jewish (ASJ) AF: 0.00236 AC: 51 AN: 21602

East Asian (EAS) AF: 0.00 AC: 0 AN: 25504

South Asian (SAS) AF: 0.00 AC: 0 AN: 77276

European-Finnish (FIN) AF: 0.00171 AC: 38 AN: 22160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5120

European-Non Finnish (NFE) AF: 0.000927 AC: 937 AN: 1010976

Other (OTH) AF: 0.000824 AC: 42 AN: 50948

GnomAD4 genome AF: 0.00102 AC: 155 AN: 151516 Hom.: 0 Cov.: 32 AF XY: 0.000920 AC XY: 68 AN XY: 73928

African (AFR) AF: 0.0000728 AC: 3 AN: 41184

American (AMR) AF: 0.000789 AC: 12 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00125 AC: 13 AN: 10370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00175 AC: 119 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00161 Hom.: 0

Bravo AF: 0.000718

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.88
PhyloP100		0.23
Mutation Taster		=97/3	polymorphism

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: rs557013417; hg19: chr1-22405305;