2-37646352-G-A

Variant names:

• chr2-37646352-G-A
• NM_006449.5:c.236C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006449.5(CDC42EP3):​c.236C>T​(p.Pro79Leu) 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. 15/22 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: CDC42EP3 NM_006449.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52
• Publications: 0 publications found

Genes affected

CDC42EP3 (HGNC:16943): (CDC42 effector protein 3) This gene encodes a member of a small family of guanosine triphosphate (GTP) metabolizing proteins that contain a CRIB (Cdc42, Rac interactive binding) domain. Members of this family of proteins act as effectors of CDC42 function. The encoded protein is involved in actin cytoskeleton re-organization during cell shape changes, including pseudopodia formation. A pseudogene of this gene is found on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

CDC42EP3-AS1 (HGNC:56370): (CDC42EP3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26357552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC42EP3	NM_006449.5	c.236C>T	p.Pro79Leu	missense_variant	Exon 2 of 2	ENST00000295324.4	NP_006440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42EP3	ENST00000295324.4	c.236C>T	p.Pro79Leu	missense_variant	Exon 2 of 2	1	NM_006449.5	ENSP00000295324.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.236C>T (p.P79L) alteration is located in exon 2 (coding exon 1) of the CDC42EP3 gene. This alteration results from a C to T substitution at nucleotide position 236, causing the proline (P) at amino acid position 79 to be replaced by a leucine (L). 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	0.082
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;T
Eigen	Benign	0.017
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.84	T;.;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.0	L;L;.
PhyloP100		1.5
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.7	.;N;N
REVEL	Benign	0.26
Sift	Benign	0.15	.;T;T
Sift4G	Benign	0.31	T;T;.
Polyphen		0.41	B;B;.
Vest4		0.21
MutPred		0.40		Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);Loss of disorder (P = 0.0353);
MVP		0.92
MPC		0.18
ClinPred		0.51	D
GERP RS		5.8
Varity_R		0.083
gMVP		0.40
Mutation Taster		=86/14	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

hg19: chr2-37873495;