chr14-102933762-T-C

Position:

chr14-102933762-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_006035.4(CDC42BPB):c.5086A>G(p.Arg1696Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000002 in 1,498,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CDC42BPB
NM_006035.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

Variant links:

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]

CDC42BPB links:

ENSG00000259515 (HGNC:):

ENSG00000259515 links:

Genome browser will be placed here

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 in gene, where missense usually causes diseases (based on misZ statistic), CDC42BPB. . Gene score misZ 3.6598 (greater than the threshold 3.09). Trascript score misZ 3.9995 (greater than threshold 3.09). GenCC has associacion of gene with Chilton-Okur-Chung neurodevelopmental syndrome, complex neurodevelopmental disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.24618194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42BPB	NM_006035.4 linkuse as main transcript	c.5086A>G	p.Arg1696Gly	missense_variant	37/37	ENST00000361246.7	NP_006026.3	Q9Y5S2A0A024R6N2Q86XZ8
CDC42BPB	NM_001411054.1 linkuse as main transcript	c.5008A>G	p.Arg1670Gly	missense_variant	36/36		NP_001397983.1
CDC42BPB	XM_005268227.2 linkuse as main transcript	c.5137A>G	p.Arg1713Gly	missense_variant	38/38		XP_005268284.1
CDC42BPB	XM_005268228.2 linkuse as main transcript	c.5059A>G	p.Arg1687Gly	missense_variant	37/37		XP_005268285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDC42BPB	ENST00000361246.7 linkuse as main transcript	c.5086A>G	p.Arg1696Gly	missense_variant	37/37	1	NM_006035.4	ENSP00000355237.2	Q9Y5S2
CDC42BPB	ENST00000559043.2 linkuse as main transcript	c.5008A>G	p.Arg1670Gly	missense_variant	36/36	5		ENSP00000453384.2	H0YLY0
ENSG00000259515	ENST00000560931.1 linkuse as main transcript	n.189T>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

150996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000148

AC:

AN:

1347740

Hom.:

Cov.:

AF XY:

0.00000300

AC XY:

AN XY:

666412

show subpopulations

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:

0.0000297

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000662

AC:

AN:

150996

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73666

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Oct 09, 2024

The c.5086A>G (p.R1696G) alteration is located in exon 37 (coding exon 37) of the CDC42BPB gene. This alteration results from a A to G substitution at nucleotide position 5086, causing the arginine (R) at amino acid position 1696 to be replaced by a glycine (G). 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

0.28

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.0

REVEL

Uncertain

0.33

Sift

Benign

0.095

Sift4G

Benign

0.17

Polyphen

0.97

Vest4

0.47

MutPred

0.16

Loss of glycosylation at P1694 (P = 0.062);

MVP

0.67

MPC

1.5

ClinPred

0.95

GERP RS

-0.37

Varity_R

0.20

gMVP

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over