14-102938171-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_006035.4(CDC42BPB):āc.4937G>Cā(p.Gly1646Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
CDC42BPB
NM_006035.4 missense
NM_006035.4 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 4.22
Genes affected
CDC42BPB (HGNC:1738): (CDC42 binding protein kinase beta) This gene encodes a member of the serine/threonine protein kinase family. The encoded protein contains a Cdc42/Rac-binding p21 binding domain resembling that of PAK kinase. The kinase domain of this protein is most closely related to that of myotonic dystrophy kinase-related ROK. Studies of the similar gene in rat suggested that this kinase may act as a downstream effector of Cdc42 in cytoskeletal reorganization. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, CDC42BPB
BP4
Computational evidence support a benign effect (MetaRNN=0.16431904).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDC42BPB | NM_006035.4 | c.4937G>C | p.Gly1646Ala | missense_variant | 36/37 | ENST00000361246.7 | |
CDC42BPB | NM_001411054.1 | c.4859G>C | p.Gly1620Ala | missense_variant | 35/36 | ||
CDC42BPB | XM_005268227.2 | c.4988G>C | p.Gly1663Ala | missense_variant | 37/38 | ||
CDC42BPB | XM_005268228.2 | c.4910G>C | p.Gly1637Ala | missense_variant | 36/37 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDC42BPB | ENST00000361246.7 | c.4937G>C | p.Gly1646Ala | missense_variant | 36/37 | 1 | NM_006035.4 | P1 | |
CDC42BPB | ENST00000559043.2 | c.4859G>C | p.Gly1620Ala | missense_variant | 35/36 | 5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250284Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135282
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461112Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726874
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 14, 2023 | The c.4937G>C (p.G1646A) alteration is located in exon 36 (coding exon 36) of the CDC42BPB gene. This alteration results from a G to C substitution at nucleotide position 4937, causing the glycine (G) at amino acid position 1646 to be replaced by an alanine (A). Based on data from gnomAD, the C allele has an overall frequency of 0.001% (2/250284) total alleles studied. The highest observed frequency was 0.006% (1/16246) of African alleles. This amino acid position is well conserved in available vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at