rs2802269

Variant names:

• chr1-226994332-G-A
• rs2802269
• NM_001394014.1:c.5201C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000366766.8(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. 16/21 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 ENST00000366766.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 26 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000366766.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42BPA	NM_001394014.1	MANE Select	c.5201C>T	p.Ala1734Val	missense	Exon 37 of 37	NP_001380943.1
	CDC42BPA	NM_001387550.1		c.5474C>T	p.Ala1825Val	missense	Exon 40 of 40	NP_001374479.1
	CDC42BPA	NM_001366019.2		c.5135C>T	p.Ala1712Val	missense	Exon 37 of 37	NP_001352948.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC42BPA	ENST00000366766.8	TSL:5 MANE Select	c.5201C>T	p.Ala1734Val	missense	Exon 37 of 37	ENSP00000355728.5
	CDC42BPA	ENST00000366769.7	TSL:1	c.5096C>T	p.Ala1699Val	missense	Exon 36 of 36	ENSP00000355731.3
	CDC42BPA	ENST00000366764.8	TSL:1	c.5036C>T	p.Ala1679Val	missense	Exon 36 of 36	ENSP00000355726.5

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

GnomAD2 exomes AF: 0.888 AC: 198183 AN: 223264 AF XY: 0.883

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 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

African (AFR) AF: 0.909 AC: 30183 AN: 33192

American (AMR) AF: 0.892 AC: 38366 AN: 42998

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 23401 AN: 25672

East Asian (EAS) AF: 0.890 AC: 34941 AN: 39280

South Asian (SAS) AF: 0.813 AC: 68129 AN: 83796

European-Finnish (FIN) AF: 0.928 AC: 48605 AN: 52368

Middle Eastern (MID) AF: 0.825 AC: 4733 AN: 5738

European-Non Finnish (NFE) AF: 0.897 AC: 989118 AN: 1102698

Other (OTH) AF: 0.896 AC: 53486 AN: 59668

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

African (AFR) AF: 0.911 AC: 37797 AN: 41474

American (AMR) AF: 0.897 AC: 13724 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3160 AN: 3472

East Asian (EAS) AF: 0.893 AC: 4596 AN: 5148

South Asian (SAS) AF: 0.824 AC: 3953 AN: 4796

European-Finnish (FIN) AF: 0.935 AC: 9914 AN: 10604

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.895 AC: 60824 AN: 67964

Other (OTH) AF: 0.883 AC: 1866 AN: 2114

Alfa AF: 0.895 Hom.: 184047

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 v4.9

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
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	5.5e-7	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.41	N
PhyloP100		2.0
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.074
Sift	Benign	1.0	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.029
MPC		0.24
ClinPred		0.0023	T
GERP RS		1.2
Varity_R		0.026
gMVP		0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs2802269; hg19: chr1-227182033; COSMIC: COSV104634407; COSMIC: COSV104634407;