11-64826489-G-C

Position:

• chr11-64826489-G-C

Variant summary

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

The NM_017525.3(CDC42BPG):​c.4580C>G​(p.Pro1527Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,048 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CDC42BPG NM_017525.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.88

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42BPG	NM_017525.3	c.4580C>G	p.Pro1527Arg	missense_variant	36/37	ENST00000342711.6	NP_059995.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42BPG	ENST00000342711.6	c.4580C>G	p.Pro1527Arg	missense_variant	36/37	1	NM_017525.3	ENSP00000345133.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449048 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 719362

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

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 13, 2022

The c.4580C>G (p.P1527R) alteration is located in exon 36 (coding exon 36) of the CDC42BPG gene. This alteration results from a C to G substitution at nucleotide position 4580, causing the proline (P) at amino acid position 1527 to be replaced by an arginine (R). 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	0.098
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.096	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Uncertain	0.25	D
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.13	T
Polyphen		0.99	D
Vest4		0.39
MutPred		0.27		Gain of MoRF binding (P = 0.0059);
MVP		0.88
MPC		0.90
ClinPred		0.94	D
GERP RS		4.9
Varity_R		0.28
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-64593961;