11-65321418-C-G

Variant names:

• chr11-65321418-C-G
• NM_006779.4:c.520C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006779.4(CDC42EP2):​c.520C>G​(p.Leu174Val) 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. 14/21 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: CDC42EP2 NM_006779.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.129

Genes affected

CDC42EP2 (HGNC:16263): (CDC42 effector protein 2) CDC42, a small Rho GTPase, regulates the formation of F-actin-containing structures through its interaction with the downstream effector proteins. The protein encoded by this gene is a member of the Borg family of CDC42 effector proteins. Borg family proteins contain a CRIB (Cdc42/Rac interactive-binding) domain. They bind to, and negatively regulate the function of CDC42. Coexpression of this protein with CDC42 suggested a role of this protein in actin filament assembly and cell shape control. [provided by RefSeq, Aug 2011]

ENSG00000285816 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059822947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC42EP2	NM_006779.4	c.520C>G	p.Leu174Val	missense_variant	Exon 2 of 2	ENST00000279249.3	NP_006770.1
CDC42EP2	XM_047426244.1	c.520C>G	p.Leu174Val	missense_variant	Exon 2 of 2		XP_047282200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42EP2	ENST00000279249.3	c.520C>G	p.Leu174Val	missense_variant	Exon 2 of 2	1	NM_006779.4	ENSP00000279249.2
ENSG00000285816	ENST00000649896.1	n.*846C>G		non_coding_transcript_exon_variant	Exon 19 of 20			ENSP00000498025.1
ENSG00000285816	ENST00000649896.1	n.*846C>G		3_prime_UTR_variant	Exon 19 of 20			ENSP00000498025.1
CDC42EP2	ENST00000533419.1	c.520C>G	p.Leu174Val	missense_variant	Exon 2 of 2	3		ENSP00000431660.1

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

Feb 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.520C>G (p.L174V) alteration is located in exon 2 (coding exon 1) of the CDC42EP2 gene. This alteration results from a C to G substitution at nucleotide position 520, causing the leucine (L) at amino acid position 174 to be replaced by a valine (V). 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	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.71
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.66	.;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.11
Sift	Benign	0.30	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.0090	B;B
Vest4		0.044
MutPred		0.36		Gain of glycosylation at S175 (P = 0.0936);Gain of glycosylation at S175 (P = 0.0936);
MVP		0.22
ClinPred		0.11	T
GERP RS		2.1
Varity_R		0.084
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65088889;