rs2282168

Variant names:

• chr9-120407440-C-G
• rs2282168
• NM_018249.6:c.4727-192G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-120407440-C-G
• chr9-120407440-C-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_018249.6(CDK5RAP2):​c.4727-192G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 620,264 control chromosomes in the GnomAD database, including 201,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (49705 hom., cov: 32)
  • Exomes 𝑓: 0.80 (151314 hom.)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.806
• Publications: 5 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 9-120407440-C-G is Benign according to our data. Variant chr9-120407440-C-G is described in ClinVar as Benign. ClinVar VariationId is 678319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.854 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.4727-192G>C		intron	N/A	NP_060719.4
	CDK5RAP2	NM_001410994.1		c.4724-192G>C		intron	N/A	NP_001397923.1	A0A8I5QKL1
	CDK5RAP2	NM_001410993.1		c.4631-192G>C		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.4727-192G>C		intron	N/A	ENSP00000343818.4	Q96SN8-1
	CDK5RAP2	ENST00000360190.8	TSL:1	c.4726+907G>C		intron	N/A	ENSP00000353317.4	Q96SN8-4
	CDK5RAP2	ENST00000483412.5	TSL:1	n.4941G>C		non_coding_transcript_exon	Exon 24 of 24

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122707 AN: 152054 Hom.: 49664 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.805

GnomAD4 exome AF: 0.803 AC: 375856 AN: 468092 Hom.: 151314 Cov.: 4 AF XY: 0.804 AC XY: 199266 AN XY: 247828

African (AFR) AF: 0.821 AC: 10764 AN: 13110

American (AMR) AF: 0.891 AC: 21413 AN: 24034

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 11440 AN: 15042

East Asian (EAS) AF: 0.883 AC: 27365 AN: 30978

South Asian (SAS) AF: 0.832 AC: 40496 AN: 48650

European-Finnish (FIN) AF: 0.844 AC: 25373 AN: 30062

Middle Eastern (MID) AF: 0.788 AC: 1784 AN: 2264

European-Non Finnish (NFE) AF: 0.778 AC: 215648 AN: 277114

Other (OTH) AF: 0.804 AC: 21573 AN: 26838

GnomAD4 genome AF: 0.807 AC: 122806 AN: 152172 Hom.: 49705 Cov.: 32 AF XY: 0.811 AC XY: 60381 AN XY: 74412

African (AFR) AF: 0.819 AC: 34005 AN: 41506

American (AMR) AF: 0.849 AC: 12984 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2631 AN: 3472

East Asian (EAS) AF: 0.876 AC: 4536 AN: 5180

South Asian (SAS) AF: 0.830 AC: 4005 AN: 4824

European-Finnish (FIN) AF: 0.860 AC: 9107 AN: 10586

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52812 AN: 67994

Other (OTH) AF: 0.807 AC: 1702 AN: 2108

Alfa AF: 0.704 Hom.: 2018

Bravo AF: 0.811

Asia WGS AF: 0.888 AC: 3087 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.64
PhyloP100		0.81
Mutation Taster		=100/0	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: rs2282168; hg19: chr9-123169718;