rs13287599

Variant names:

• chr9-120536488-A-C
• rs13287599
• NM_018249.6:c.546T>G

Your query was ambiguous. Multiple possible variants found:

• chr9-120536488-A-C
• chr9-120536488-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018249.6(CDK5RAP2):​c.546T>G​(p.Phe182Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Synonymous variant affecting the same amino acid position (i.e. F182F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK5RAP2 NM_018249.6 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 3.83
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive primary microcephaly

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• microcephaly 3, primary, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• corpus callosum, agenesis of

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11035693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5RAP2	NM_018249.6	c.546T>G	p.Phe182Leu	missense_variant	Exon 7 of 38	ENST00000349780.9	NP_060719.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.546T>G	p.Phe182Leu	missense_variant	Exon 7 of 38	1	NM_018249.6	ENSP00000343818.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Microcephaly 3, primary, autosomal recessive Other:1

-

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.14	.;T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	.;L;L
PhyloP100		3.8
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.057
Sift	Benign	0.37	T;T;T
Sift4G	Benign	0.54	T;T;T
Polyphen		0.053, 0.0030	.;B;B
Vest4		0.17
MutPred		0.15		Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);Gain of loop (P = 0.1081);
MVP		0.22
MPC		0.13
ClinPred		0.18	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.053
gMVP		0.25
Mutation Taster		=78/22	polymorphism

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: rs13287599; hg19: chr9-123298766;