rs2069459

Variant names:

• chr7-151054503-C-A
• rs2069459
• NM_004935.4:c.651-38G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-151054503-C-A
• chr7-151054503-C-G
• chr7-151054503-C-T

Variant summary

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

The NM_004935.4(CDK5):​c.651-38G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,584,148 control chromosomes in the GnomAD database, including 108,437 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 0.38 (11364 hom., cov: 31)
  • Exomes 𝑓: 0.37 (97073 hom.)
• Consequence: CDK5 NM_004935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 24 publications found

Genes affected

CDK5 (HGNC:1774): (cyclin dependent kinase 5) This gene encodes a proline-directed serine/threonine kinase that is a member of the cyclin-dependent kinase family of proteins. Unlike other members of the family, the protein encoded by this gene does not directly control cell cycle regulation. Instead the protein, which is predominantly expressed at high levels in mammalian postmitotic central nervous system neurons, functions in diverse processes such as synaptic plasticity and neuronal migration through phosphorylation of proteins required for cytoskeletal organization, endocytosis and exocytosis, and apoptosis. In humans, an allelic variant of the gene that results in undetectable levels of the protein has been associated with lethal autosomal recessive lissencephaly-7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

CDK5 Gene-Disease associations (from GenCC):

• lissencephaly 7 with cerebellar hypoplasia

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5	NM_004935.4	c.651-38G>T		intron_variant	Intron 9 of 11	ENST00000485972.6	NP_004926.1
CDK5	NM_001164410.3	c.555-38G>T		intron_variant	Intron 8 of 10		NP_001157882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5	ENST00000485972.6	c.651-38G>T		intron_variant	Intron 9 of 11	1	NM_004935.4	ENSP00000419782.1
CDK5	ENST00000297518.4	c.555-38G>T		intron_variant	Intron 8 of 10	1		ENSP00000297518.4

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58120 AN: 151724 Hom.: 11362 Cov.: 31

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.386

GnomAD2 exomes AF: 0.355 AC: 82337 AN: 232218 AF XY: 0.358

Gnomad AFR exome AF: 0.426

Gnomad AMR exome AF: 0.221

Gnomad ASJ exome AF: 0.422

Gnomad EAS exome AF: 0.355

Gnomad FIN exome AF: 0.431

Gnomad NFE exome AF: 0.367

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.366 AC: 524158 AN: 1432306 Hom.: 97073 Cov.: 28 AF XY: 0.366 AC XY: 259782 AN XY: 710318

African (AFR) AF: 0.423 AC: 13963 AN: 32988

American (AMR) AF: 0.228 AC: 9875 AN: 43234

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 10199 AN: 24488

East Asian (EAS) AF: 0.374 AC: 14718 AN: 39388

South Asian (SAS) AF: 0.345 AC: 28605 AN: 82980

European-Finnish (FIN) AF: 0.424 AC: 22245 AN: 52480

Middle Eastern (MID) AF: 0.356 AC: 2010 AN: 5640

European-Non Finnish (NFE) AF: 0.367 AC: 400289 AN: 1092018

Other (OTH) AF: 0.377 AC: 22254 AN: 59090

GnomAD4 genome AF: 0.383 AC: 58160 AN: 151842 Hom.: 11364 Cov.: 31 AF XY: 0.385 AC XY: 28535 AN XY: 74206

African (AFR) AF: 0.419 AC: 17346 AN: 41380

American (AMR) AF: 0.329 AC: 5023 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1420 AN: 3466

East Asian (EAS) AF: 0.361 AC: 1847 AN: 5122

South Asian (SAS) AF: 0.341 AC: 1640 AN: 4806

European-Finnish (FIN) AF: 0.433 AC: 4579 AN: 10574

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25109 AN: 67896

Other (OTH) AF: 0.386 AC: 814 AN: 2108

Alfa AF: 0.370 Hom.: 44384

Bravo AF: 0.375

Asia WGS AF: 0.338 AC: 1175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.48
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2069459; hg19: chr7-150751590; COSMIC: COSV52520297; COSMIC: COSV52520297;