22-37566587-A-G

Position:

• chr22-37566587-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152243.3(CDC42EP1):​c.238A>G​(p.Ser80Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDC42EP1 NM_152243.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89

Genes affected

CDC42EP1 (HGNC:17014): (CDC42 effector protein 1) CDC42 is a member of the Rho GTPase family that regulates multiple cellular activities, including actin polymerization. The protein encoded by this gene is a CDC42 binding protein that mediates actin cytoskeleton reorganization at the plasma membrane. This protein is secreted and is primarily found in bone marrow. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.091861844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42EP1	NM_152243.3	c.238A>G	p.Ser80Gly	missense_variant	2/3	ENST00000249014.5	NP_689449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42EP1	ENST00000249014.5	c.238A>G	p.Ser80Gly	missense_variant	2/3	1	NM_152243.3	ENSP00000249014.4
CDC42EP1	ENST00000430687.1	c.*28A>G		downstream_gene_variant		3		ENSP00000411682.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000413 AC: 1 AN: 242346 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 131272

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000921

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

The c.238A>G (p.S80G) alteration is located in exon 2 (coding exon 1) of the CDC42EP1 gene. This alteration results from a A to G substitution at nucleotide position 238, causing the serine (S) at amino acid position 80 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Benign	0.87
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.43	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.040
Sift	Benign	0.24	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.41		Loss of phosphorylation at S80 (P = 0.0281);
MVP		0.45
MPC		0.045
ClinPred		0.021	T
GERP RS		1.9
Varity_R		0.046
gMVP		0.33

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: rs754285888; hg19: chr22-37962594;