rs7859743

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-120394313-A-G
• chr9-120394313-A-C

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 VariationId 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.

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.5578+199T>C		intron	N/A	NP_060719.4
	CDK5RAP2	NM_001410994.1		c.5575+199T>C		intron	N/A	NP_001397923.1	A0A8I5QKL1
	CDK5RAP2	NM_001410993.1		c.5482+199T>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.5578+199T>C		intron	N/A	ENSP00000343818.4	Q96SN8-1
	CDK5RAP2	ENST00000360190.8	TSL:1	c.5341+199T>C		intron	N/A	ENSP00000353317.4	Q96SN8-4
	CDK5RAP2	ENST00000473282.6	TSL:1	n.*4402+199T>C		intron	N/A	ENSP00000419265.1	F8WF55

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

African (AFR) AF: 0.584 AC: 24167 AN: 41404

American (AMR) AF: 0.728 AC: 11123 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2269 AN: 3470

East Asian (EAS) AF: 0.798 AC: 4116 AN: 5156

South Asian (SAS) AF: 0.664 AC: 3189 AN: 4802

European-Finnish (FIN) AF: 0.777 AC: 8223 AN: 10578

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46252 AN: 67960

Other (OTH) AF: 0.670 AC: 1413 AN: 2108

Alfa AF: 0.674 Hom.: 69606

Bravo AF: 0.664

Asia WGS AF: 0.751 AC: 2612 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		-0.34
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: rs7859743; hg19: chr9-123156591; COSMIC: COSV62578564; COSMIC: COSV62578564;