NM_018249.6:c.5578+199T>C

Variant names:

• chr9-120394313-A-G
• rs7859743
• NM_018249.6:c.5578+199T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018249.6(CDK5RAP2):​c.5578+199T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 151,966 control chromosomes in the GnomAD database, including 34,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.67 (34205 hom., cov: 32)
• Consequence: CDK5RAP2 NM_018249.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.338

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-120394313-A-G is Benign according to our data. Variant chr9-120394313-A-G is described in ClinVar as [Benign]. Clinvar id is 678321.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5RAP2	NM_018249.6	c.5578+199T>C		intron_variant	Intron 36 of 37	ENST00000349780.9	NP_060719.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5RAP2	ENST00000349780.9	c.5578+199T>C		intron_variant	Intron 36 of 37	1	NM_018249.6	ENSP00000343818.4

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101375 AN: 151848 Hom.: 34182 Cov.: 32

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.670

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.668 AC: 101443 AN: 151966 Hom.: 34205 Cov.: 32 AF XY: 0.672 AC XY: 49924 AN XY: 74270

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.670

Alfa AF: 0.681 Hom.: 51350

Bravo AF: 0.664

Asia WGS AF: 0.751 AC: 2612 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.53

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: rs7859743; hg19: chr9-123156591; COSMIC: COSV62578564; COSMIC: COSV62578564;