11-64827366-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017525.3(CDC42BPG):c.4183G>C(p.Asp1395His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDC42BPG NM_017525.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.76

Genes affected

CDC42BPG (HGNC:29829): (CDC42 binding protein kinase gamma) Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in protein phosphorylation. Located in cell leading edge; centriolar satellite; and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC42BPG	NM_017525.3	c.4183G>C	p.Asp1395His	missense_variant	33/37	ENST00000342711.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC42BPG	ENST00000342711.6	c.4183G>C	p.Asp1395His	missense_variant	33/37	1	NM_017525.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Feb 28, 2023

The c.4183G>C (p.D1395H) alteration is located in exon 33 (coding exon 33) of the CDC42BPG gene. This alteration results from a G to C substitution at nucleotide position 4183, causing the aspartic acid (D) at amino acid position 1395 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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	0.097	D
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.048	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.32		Gain of MoRF binding (P = 0.0674);
MVP		0.82
MPC		0.95
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.49
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr11-64594838;