rs2069454

Variant names:

• chr7-151055895-C-G
• rs2069454
• NM_004935.4:c.313-47G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-151055895-C-G
• chr7-151055895-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.313-47G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.046 in 1,325,908 control chromosomes in the GnomAD database, including 1,541 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 0.047 (227 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1314 hom.)
• Consequence: CDK5 NM_004935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 12 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• lissencephaly with cerebellar hypoplasia

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0651 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004935.4. 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
	CDK5	NM_004935.4	MANE Select	c.313-47G>C		intron	N/A	NP_004926.1	A0A090N7W4
	CDK5	NM_001164410.3		c.313-289G>C		intron	N/A	NP_001157882.1	A0A0S2Z355

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK5	ENST00000485972.6	TSL:1 MANE Select	c.313-47G>C		intron	N/A	ENSP00000419782.1	Q00535-1
	CDK5	ENST00000297518.4	TSL:1	c.313-289G>C		intron	N/A	ENSP00000297518.4	Q00535-2
	CDK5	ENST00000891064.1		c.349-47G>C		intron	N/A	ENSP00000561123.1

Frequencies

GnomAD3 genomes AF: 0.0474 AC: 7217 AN: 152184 Hom.: 229 Cov.: 32

Gnomad AFR AF: 0.0671

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0334

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.00981

Gnomad SAS AF: 0.0524

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0402

GnomAD2 exomes AF: 0.0406 AC: 7201 AN: 177296 AF XY: 0.0422

Gnomad AFR exome AF: 0.0685

Gnomad AMR exome AF: 0.0225

Gnomad ASJ exome AF: 0.0340

Gnomad EAS exome AF: 0.00953

Gnomad FIN exome AF: 0.0266

Gnomad NFE exome AF: 0.0473

Gnomad OTH exome AF: 0.0392

GnomAD4 exome AF: 0.0458 AC: 53778 AN: 1173606 Hom.: 1314 Cov.: 16 AF XY: 0.0463 AC XY: 27334 AN XY: 590730

African (AFR) AF: 0.0694 AC: 1914 AN: 27592

American (AMR) AF: 0.0243 AC: 901 AN: 37060

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 851 AN: 23866

East Asian (EAS) AF: 0.0104 AC: 377 AN: 36090

South Asian (SAS) AF: 0.0608 AC: 4586 AN: 75470

European-Finnish (FIN) AF: 0.0303 AC: 1516 AN: 50078

Middle Eastern (MID) AF: 0.0536 AC: 283 AN: 5284

European-Non Finnish (NFE) AF: 0.0474 AC: 41104 AN: 867274

Other (OTH) AF: 0.0441 AC: 2246 AN: 50892

GnomAD4 genome AF: 0.0474 AC: 7224 AN: 152302 Hom.: 227 Cov.: 32 AF XY: 0.0466 AC XY: 3469 AN XY: 74470

African (AFR) AF: 0.0672 AC: 2792 AN: 41564

American (AMR) AF: 0.0333 AC: 510 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0377 AC: 131 AN: 3472

East Asian (EAS) AF: 0.00983 AC: 51 AN: 5186

South Asian (SAS) AF: 0.0524 AC: 253 AN: 4826

European-Finnish (FIN) AF: 0.0298 AC: 317 AN: 10622

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0445 AC: 3025 AN: 68010

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0430 Hom.: 25

Bravo AF: 0.0478

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.73
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2069454; hg19: chr7-150752982; COSMIC: COSV52523827;