14-102933764-T-C

Position:

chr14-102933764-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_006035.4(CDC42BPB):c.5084A>G(p.His1695Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000468 in 1,495,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1695D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

CDC42BPB
NM_006035.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.90

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

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=0.25311923).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CDC42BPB	NM_006035.4 linkuse as main transcript	c.5084A>G	p.His1695Arg	missense_variant	37/37	ENST00000361246.7
CDC42BPB	NM_001411054.1 linkuse as main transcript	c.5006A>G	p.His1669Arg	missense_variant	36/36
CDC42BPB	XM_005268227.2 linkuse as main transcript	c.5135A>G	p.His1712Arg	missense_variant	38/38
CDC42BPB	XM_005268228.2 linkuse as main transcript	c.5057A>G	p.His1686Arg	missense_variant	37/37

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CDC42BPB	ENST00000361246.7 linkuse as main transcript	c.5084A>G	p.His1695Arg	missense_variant	37/37	1	NM_006035.4	P1
	ENST00000560931.1 linkuse as main transcript	n.191T>C		non_coding_transcript_exon_variant	1/2	3
CDC42BPB	ENST00000559043.2 linkuse as main transcript	c.5006A>G	p.His1669Arg	missense_variant	36/36	5

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149510

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:

0.000197

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000315

AC:

AN:

127116

Hom.:

AF XY:

0.0000282

AC XY:

AN XY:

70838

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000339

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000684

Gnomad NFE exome

AF:

0.0000151

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000446

AC:

AN:

1346358

Hom.:

Cov.:

AF XY:

0.00000601

AC XY:

AN XY:

665720

show subpopulations

Gnomad4 AFR exome

AF:

0.0000374

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000177

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000180

GnomAD4 genome

AF:

0.00000669

AC:

AN:

149510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72822

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000197

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000435

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000834

AC:

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

Dec 18, 2023

The c.5084A>G (p.H1695R) 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 5084, causing the histidine (H) at amino acid position 1695 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

0.21

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.069

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.058

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.4

REVEL

Benign

0.25

Sift

Uncertain

0.0060

Sift4G

Benign

0.40

Polyphen

0.96

Vest4

0.44

MutPred

0.21

Gain of solvent accessibility (P = 0.0074);

MVP

0.72

MPC

1.1

ClinPred

0.30

GERP RS

3.7

Varity_R

0.22

gMVP

0.49

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

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