NM_001394014.1:c.5248G>C

Variant names:

• chr1-226994285-C-G
• NM_001394014.1:c.5248G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394014.1(CDC42BPA):​c.5248G>C​(p.Gly1750Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,433,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CDC42BPA NM_001394014.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13058102).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC42BPA	NM_001394014.1	c.5248G>C	p.Gly1750Arg	missense_variant	Exon 37 of 37	ENST00000366766.8	NP_001380943.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC42BPA	ENST00000366766.8	c.5248G>C	p.Gly1750Arg	missense_variant	Exon 37 of 37	5	NM_001394014.1	ENSP00000355728.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1433512 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 710408

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000260

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	.;T;.;.;T
Eigen	Benign	-0.019
Eigen_PC	Benign	0.060
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	0.0	.;N;.;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.90	N;.;N;.;.
REVEL	Benign	0.073
Sift	Benign	0.057	T;.;T;.;.
Sift4G	Benign	0.55	T;T;T;T;T
Polyphen		0.58	P;.;P;.;.
Vest4		0.094
MutPred		0.19		.;.;.;.;Gain of MoRF binding (P = 0.0087);
MVP		0.42
MPC		0.28
ClinPred		0.41	T
GERP RS		4.2
Varity_R		0.12
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-227181986;