chr14-102938127-G-C

Variant names:

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

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>G​(p.Pro1661Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,632 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1661T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CDC42BPB NM_006035.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.23072812).

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>G	p.Pro1661Ala	missense	Exon 36 of 37	NP_006026.3
	CDC42BPB	NM_001411054.1		c.4903C>G	p.Pro1635Ala	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>G	p.Pro1661Ala	missense	Exon 36 of 37	ENSP00000355237.2	Q9Y5S2
	CDC42BPB	ENST00000901190.1		c.4960C>G	p.Pro1654Ala	missense	Exon 36 of 37	ENSP00000571249.1
	CDC42BPB	ENST00000901191.1		c.4954C>G	p.Pro1652Ala	missense	Exon 36 of 37	ENSP00000571250.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461632 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727110

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.062	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.1
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Uncertain	0.010	D
Sift4G	Benign	0.093	T
Polyphen		0.11	B
Vest4		0.31
MutPred		0.19		Loss of stability (P = 0.1456)
MVP		0.56
MPC		0.48
ClinPred		0.72	D
GERP RS		4.3
Varity_R		0.077
gMVP		0.30
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs1382376082; hg19: chr14-103404464;