1-226994897-G-A

Variant names:

• chr1-226994897-G-A
• rs772385104
• NM_001394014.1:c.5059C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001394014.1(CDC42BPA):​c.5059C>T​(p.Pro1687Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P1687T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDC42BPA NM_001394014.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.29
• Publications: 0 publications found

Genes affected

CDC42BPA (HGNC:1737): (CDC42 binding protein kinase alpha) The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase contains multiple functional domains. Its kinase domain is highly similar to that of the myotonic dystrophy protein kinase (DMPK). This kinase also contains a Rac interactive binding (CRIB) domain, and has been shown to bind CDC42. It may function as a CDC42 downstream effector mediating CDC42 induced peripheral actin formation, and promoting cytoskeletal reorganization. Multiple alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2018]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3179285).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394014.1. 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
	CDC42BPA	NM_001394014.1	MANE Select	c.5059C>T	p.Pro1687Ser	missense	Exon 36 of 37	NP_001380943.1	Q5VT25-2
	CDC42BPA	NM_001387550.1		c.5332C>T	p.Pro1778Ser	missense	Exon 39 of 40	NP_001374479.1	A0A0A0MRJ1
	CDC42BPA	NM_001366019.2		c.4993C>T	p.Pro1665Ser	missense	Exon 36 of 37	NP_001352948.1	Q5VT25-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42BPA	ENST00000366766.8	TSL:5 MANE Select	c.5059C>T	p.Pro1687Ser	missense	Exon 36 of 37	ENSP00000355728.5	Q5VT25-2
	CDC42BPA	ENST00000366769.7	TSL:1	c.4954C>T	p.Pro1652Ser	missense	Exon 35 of 36	ENSP00000355731.3	Q5VT25-5
	CDC42BPA	ENST00000366764.8	TSL:1	c.4894C>T	p.Pro1632Ser	missense	Exon 35 of 36	ENSP00000355726.5	A0A0A0MRJ0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.5	L
PhyloP100		9.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.31
Sift	Benign	0.050	D
Sift4G	Benign	0.83	T
Polyphen		1.0	D
Vest4		0.57
MutPred		0.29		Gain of phosphorylation at P1632 (P = 0.0024)
MVP		0.43
MPC		0.87
ClinPred		0.95	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.069
gMVP		0.48
Mutation Taster		=57/43	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: rs772385104; hg19: chr1-227182598; COSMIC: COSV106443841; COSMIC: COSV106443841;