rs7875294

Positions:

• chr9-120422708-T-A

Variant summary

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

The NM_018249.6(CDK5RAP2):​c.3989A>T​(p.Asn1330Ile) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDK5RAP2 NM_018249.6 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.487

Genes affected

CDK5RAP2 (HGNC:18672): (CDK5 regulatory subunit associated protein 2) This gene encodes a regulator of CDK5 (cyclin-dependent kinase 5) activity. The protein encoded by this gene is localized to the centrosome and Golgi complex, interacts with CDK5R1 and pericentrin (PCNT), plays a role in centriole engagement and microtubule nucleation, and has been linked to primary microcephaly and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

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=0.116322994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK5RAP2	NM_018249.6	c.3989A>T	p.Asn1330Ile	missense_variant	26/38	ENST00000349780.9	NP_060719.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.3989A>T	p.Asn1330Ile	missense_variant	26/38	1	NM_018249.6	ENSP00000343818.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Microcephaly 3, primary, autosomal recessive Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Uncertain	0.97
DEOGEN2	Uncertain	0.58	.;D;.;.;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.53	T;T;T;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	.;M;M;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-4.5	.;D;D;D;D
REVEL	Benign	0.087
Sift	Benign	0.058	.;T;D;T;T
Sift4G	Benign	0.11	T;T;T;T;T
Polyphen		0.72, 0.0, 0.92, 0.86	.;P;B;P;P
Vest4		0.20
MutPred		0.21		.;Loss of disorder (P = 0.02);Loss of disorder (P = 0.02);.;.;
MVP		0.27
MPC		0.43
ClinPred		0.97	D
GERP RS		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.089
gMVP		0.068

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: rs7875294; hg19: chr9-123184986;