5-131391069-T-A

Position:

• chr5-131391069-T-A

Variant summary

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

The NM_001375635.1(CDC42SE2):​c.233T>A​(p.Leu78His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDC42SE2 NM_001375635.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.21

Genes affected

CDC42SE2 (HGNC:18547): (CDC42 small effector 2) Enables signaling adaptor activity. Involved in regulation of signal transduction. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC42SE2	NM_001375635.1	c.233T>A	p.Leu78His	missense_variant	5/5	ENST00000505065.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC42SE2	ENST00000505065.2	c.233T>A	p.Leu78His	missense_variant	5/5	1	NM_001375635.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Dec 21, 2022

The c.233T>A (p.L78H) alteration is located in exon 5 (coding exon 3) of the CDC42SE2 gene. This alteration results from a T to A substitution at nucleotide position 233, causing the leucine (L) at amino acid position 78 to be replaced by a histidine (H). 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	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.43
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.048	T;T;T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.75	T;T;.;.
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.64	D;D;D;D
MetaSVM	Uncertain	-0.20	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.78	N;N;N;N
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.98	D;.;D;D
Vest4		0.93
MutPred		0.31		Loss of stability (P = 0.0765);.;Loss of stability (P = 0.0765);Loss of stability (P = 0.0765);
MVP		0.56
MPC		1.7
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.49
gMVP		0.57

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: chr5-130726762;