1-226994332-G-T

Position:

• chr1-226994332-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394014.1(CDC42BPA):​c.5201C>A​(p.Ala1734Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05935514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC42BPA	NM_001394014.1	c.5201C>A	p.Ala1734Asp	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>A	p.Ala1734Asp	missense_variant	37/37	5	NM_001394014.1	ENSP00000355728.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1445836 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 717670

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.064	.;T;.;.;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.80	T;T;T;T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.059	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	.;L;.;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.26	N;.;N;.;.
REVEL	Benign	0.15
Sift	Uncertain	0.0080	D;.;T;.;.
Sift4G	Benign	0.58	T;T;T;T;T
Polyphen		0.37	B;.;B;.;.
Vest4		0.11
MutPred		0.12		.;.;.;.;Loss of glycosylation at P1681 (P = 0.0885);
MVP		0.43
MPC		0.50
ClinPred		0.18	T
GERP RS		1.2
Varity_R		0.14
gMVP		0.39

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;