14-102938127-G-T

Variant names:

• chr14-102938127-G-T
• rs1382376082
• NM_006035.4:c.4981C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006035.4(CDC42BPB):​c.4981C>A​(p.Pro1661Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 6.09
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Chilton-Okur-Chung neurodevelopmental syndrome

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25791785).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006035.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42BPB	NM_006035.4	MANE Select	c.4981C>A	p.Pro1661Thr	missense	Exon 36 of 37	NP_006026.3
	CDC42BPB	NM_001411054.1		c.4903C>A	p.Pro1635Thr	missense	Exon 35 of 36	NP_001397983.1	H0YLY0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42BPB	ENST00000361246.7	TSL:1 MANE Select	c.4981C>A	p.Pro1661Thr	missense	Exon 36 of 37	ENSP00000355237.2	Q9Y5S2
	CDC42BPB	ENST00000901190.1		c.4960C>A	p.Pro1654Thr	missense	Exon 36 of 37	ENSP00000571249.1
	CDC42BPB	ENST00000901191.1		c.4954C>A	p.Pro1652Thr	missense	Exon 36 of 37	ENSP00000571250.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	0.0097	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.1
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.18
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.056	T
Polyphen		0.57	P
Vest4		0.19
MutPred		0.17		Gain of phosphorylation at P1661 (P = 0.0172)
MVP		0.52
MPC		0.48
ClinPred		0.93	D
GERP RS		4.3
Varity_R		0.15
gMVP		0.39
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs1382376082; hg19: chr14-103404464;