rs58961732

Positions:

• chr9-120572010-C-T

Variant summary

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

The NM_018249.6(CDK5RAP2):​c.91G>A​(p.Asp31Asn) 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. 13/23 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: 1.93

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]

CDK5RAP2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK5RAP2	NM_018249.6	c.91G>A	p.Asp31Asn	missense_variant	2/38	ENST00000349780.9	NP_060719.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.91G>A	p.Asp31Asn	missense_variant	2/38	1	NM_018249.6	ENSP00000343818.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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	0.081
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	.;T;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;L;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.096	T;T;T
Polyphen		0.0050, 0.76	.;B;P
Vest4		0.21
MutPred		0.12		Loss of disorder (P = 0.3329);Loss of disorder (P = 0.3329);Loss of disorder (P = 0.3329);
MVP		0.36
MPC		0.23
ClinPred		0.62	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.069
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: 31

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

Publications

LitVar

Other links and lift over

dbSNP: rs58961732; hg19: chr9-123334288; COSMIC: COSV62577419;