rs2802269

Positions:

• chr1-226994332-G-A
• chr1-226994332-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394014.1(CDC42BPA):​c.5201C>T​(p.Ala1734Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 1,597,478 control chromosomes in the GnomAD database, including 638,872 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.90 (61690 hom., cov: 30)
  • Exomes 𝑓: 0.89 (577182 hom.)
• Consequence: CDC42BPA NM_001394014.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.5291054E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42BPA	NM_001394014.1	c.5201C>T	p.Ala1734Val	missense_variant	37/37	ENST00000366766.8	NP_001380943.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC42BPA	ENST00000366766.8	c.5201C>T	p.Ala1734Val	missense_variant	37/37	5	NM_001394014.1	ENSP00000355728.5

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136800 AN: 151952 Hom.: 61641 Cov.: 30

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.882

GnomAD3 exomes AF: 0.888 AC: 198183 AN: 223264 Hom.: 88064 AF XY: 0.883 AC XY: 106340 AN XY: 120476

Gnomad AFR exome AF: 0.911

Gnomad AMR exome AF: 0.893

Gnomad ASJ exome AF: 0.910

Gnomad EAS exome AF: 0.886

Gnomad SAS exome AF: 0.814

Gnomad FIN exome AF: 0.932

Gnomad NFE exome AF: 0.893

Gnomad OTH exome AF: 0.887

GnomAD4 exome AF: 0.893 AC: 1290962 AN: 1445410 Hom.: 577182 Cov.: 43 AF XY: 0.890 AC XY: 638700 AN XY: 717414

Gnomad4 AFR exome AF: 0.909

Gnomad4 AMR exome AF: 0.892

Gnomad4 ASJ exome AF: 0.912

Gnomad4 EAS exome AF: 0.890

Gnomad4 SAS exome AF: 0.813

Gnomad4 FIN exome AF: 0.928

Gnomad4 NFE exome AF: 0.897

Gnomad4 OTH exome AF: 0.896

GnomAD4 genome AF: 0.900 AC: 136906 AN: 152068 Hom.: 61690 Cov.: 30 AF XY: 0.901 AC XY: 66989 AN XY: 74330

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.897

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 0.893

Gnomad4 SAS AF: 0.824

Gnomad4 FIN AF: 0.935

Gnomad4 NFE AF: 0.895

Gnomad4 OTH AF: 0.883

Alfa AF: 0.895 Hom.: 121694

Bravo AF: 0.896

TwinsUK AF: 0.896 AC: 3321

ALSPAC AF: 0.890 AC: 3430

ESP6500AA AF: 0.920 AC: 4053

ESP6500EA AF: 0.895 AC: 7694

ExAC AF: 0.877 AC: 105876

Asia WGS AF: 0.879 AC: 3057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	8.9
DANN	Benign	0.97
DEOGEN2	Benign	0.039	.;T;.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.35	T;T;T;T;T
MetaRNN	Benign	5.5e-7	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.41	.;N;.;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.16	N;.;N;.;.
REVEL	Benign	0.074
Sift	Benign	1.0	T;.;T;.;.
Sift4G	Benign	0.31	T;T;T;T;T
Polyphen		0.0	B;.;B;.;.
Vest4		0.029
MPC		0.24
ClinPred		0.0023	T
GERP RS		1.2
Varity_R		0.026
gMVP		0.18

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

LitVar

Other links and lift over

dbSNP: rs2802269; hg19: chr1-227182033;