chr14-102938116-G-C

Position:

• chr14-102938116-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_006035.4(CDC42BPB):​c.4992C>G​(p.Asp1664Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDC42BPB NM_006035.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.611

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]

ACMG classification

Verdict is Likely_benign. 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=0.056425184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42BPB	NM_006035.4	c.4992C>G	p.Asp1664Glu	missense_variant	36/37	ENST00000361246.7	NP_006026.3
CDC42BPB	NM_001411054.1	c.4914C>G	p.Asp1638Glu	missense_variant	35/36		NP_001397983.1
CDC42BPB	XM_005268227.2	c.5043C>G	p.Asp1681Glu	missense_variant	37/38		XP_005268284.1
CDC42BPB	XM_005268228.2	c.4965C>G	p.Asp1655Glu	missense_variant	36/37		XP_005268285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42BPB	ENST00000361246.7	c.4992C>G	p.Asp1664Glu	missense_variant	36/37	1	NM_006035.4	ENSP00000355237.2
CDC42BPB	ENST00000559043.2	c.4914C>G	p.Asp1638Glu	missense_variant	35/36	5		ENSP00000453384.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Chilton-Okur-Chung neurodevelopmental syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Department of Human Genetics, Hannover Medical School

Jan 02, 2025

ACMG: PM2_Supporting, PP2, BP4_Moderate -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Uncertain	0.97
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Benign	0.14	T
Sift4G	Benign	0.39	T
Polyphen		0.0010	B
Vest4		0.067
MutPred		0.068		Gain of helix (P = 0.1736);
MVP		0.45
MPC		0.40
ClinPred		0.25	T
GERP RS		-0.85
Varity_R		0.028
gMVP		0.098

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-103404453;