rs1888893

Variant names:

• chr9-120407793-G-A
• rs1888893
• NM_018249.6:c.4727-545C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-120407793-G-A
• chr9-120407793-G-C
• chr9-120407793-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018249.6(CDK5RAP2):​c.4727-545C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 180,586 control chromosomes in the GnomAD database, including 45,240 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (37066 hom., cov: 29)
  • Exomes 𝑓: 0.74 (8174 hom.)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.959
• Publications: 4 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• corpus callosum, agenesis of

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000301087 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018249.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK5RAP2	NM_018249.6	MANE Select	c.4727-545C>T		intron	N/A	NP_060719.4
	CDK5RAP2	NM_001410994.1		c.4724-545C>T		intron	N/A	NP_001397923.1	A0A8I5QKL1
	CDK5RAP2	NM_001410993.1		c.4631-545C>T		intron	N/A	NP_001397922.1	Q96SN8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK5RAP2	ENST00000349780.9	TSL:1 MANE Select	c.4727-545C>T		intron	N/A	ENSP00000343818.4	Q96SN8-1
	CDK5RAP2	ENST00000360190.8	TSL:1	c.4726+554C>T		intron	N/A	ENSP00000353317.4	Q96SN8-4
	CDK5RAP2	ENST00000483412.5	TSL:1	n.4588C>T		non_coding_transcript_exon	Exon 24 of 24

Frequencies

GnomAD3 genomes AF: 0.686 AC: 103983 AN: 151532 Hom.: 37068 Cov.: 29

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.713

GnomAD4 exome AF: 0.741 AC: 21446 AN: 28942 Hom.: 8174 Cov.: 0 AF XY: 0.746 AC XY: 11263 AN XY: 15104

African (AFR) AF: 0.430 AC: 226 AN: 526

American (AMR) AF: 0.835 AC: 2764 AN: 3312

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 280 AN: 422

East Asian (EAS) AF: 0.804 AC: 1398 AN: 1738

South Asian (SAS) AF: 0.796 AC: 2934 AN: 3686

European-Finnish (FIN) AF: 0.765 AC: 705 AN: 922

Middle Eastern (MID) AF: 0.777 AC: 73 AN: 94

European-Non Finnish (NFE) AF: 0.716 AC: 12045 AN: 16826

Other (OTH) AF: 0.721 AC: 1021 AN: 1416

GnomAD4 genome AF: 0.686 AC: 104022 AN: 151644 Hom.: 37066 Cov.: 29 AF XY: 0.693 AC XY: 51301 AN XY: 74080

African (AFR) AF: 0.481 AC: 19839 AN: 41274

American (AMR) AF: 0.790 AC: 12044 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2424 AN: 3468

East Asian (EAS) AF: 0.832 AC: 4279 AN: 5140

South Asian (SAS) AF: 0.816 AC: 3920 AN: 4804

European-Finnish (FIN) AF: 0.819 AC: 8570 AN: 10470

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50583 AN: 67942

Other (OTH) AF: 0.710 AC: 1489 AN: 2096

Alfa AF: 0.711 Hom.: 12556

Bravo AF: 0.687

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.72
PhyloP100		0.96
Mutation Taster		=99/1	polymorphism (auto)

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: rs1888893; hg19: chr9-123170071;