Variant chr14-102933764-T-TG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_006035.4(CDC42BPB):c.5083_5084insC(p.His1695ProfsTer16) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,346,356 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CDC42BPB
NM_006035.4 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.53

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0103 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CDC42BPB	NM_006035.4 linkuse as main transcript	c.5083_5084insC	p.His1695ProfsTer16	frameshift_variant	37/37	ENST00000361246.7
CDC42BPB	NM_001411054.1 linkuse as main transcript	c.5005_5006insC	p.His1669ProfsTer16	frameshift_variant	36/36
CDC42BPB	XM_005268227.2 linkuse as main transcript	c.5134_5135insC	p.His1712ProfsTer16	frameshift_variant	38/38
CDC42BPB	XM_005268228.2 linkuse as main transcript	c.5056_5057insC	p.His1686ProfsTer16	frameshift_variant	37/37

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CDC42BPB	ENST00000361246.7 linkuse as main transcript	c.5083_5084insC	p.His1695ProfsTer16	frameshift_variant	37/37	1	NM_006035.4	P1
	ENST00000560931.1 linkuse as main transcript	n.197dup		non_coding_transcript_exon_variant	1/2	3
CDC42BPB	ENST00000559043.2 linkuse as main transcript	c.5005_5006insC	p.His1669ProfsTer16	frameshift_variant	36/36	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000149

AC:

AN:

1346356

Hom.:

Cov.:

AF XY:

0.00000300

AC XY:

AN XY:

665720

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:

0.0000149

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.34e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Sep 08, 2022

Variant summary: CDC42BPB c.5083dupC (p.His1695ProfsX16) results in a premature termination codon in the last exon of the protein, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay. Truncations downstream of this position have not been reported in HGMD or ClinVar. The variant allele was found at a frequency of 1.6e-05 in 127116 control chromosomes. To our knowledge, no occurrence of c.5083dupC in individuals affected with Chilton-Okur Neurodevelopmental Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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