chr7-151055383-AC-A

Position:

• chr7-151055383-AC-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004935.4(CDK5):​c.484-11del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00061 in 1,602,812 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00040 (6 hom.)
• Consequence: CDK5 NM_004935.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.239

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 7-151055383-AC-A is Benign according to our data. Variant chr7-151055383-AC-A is described in ClinVar as [Benign]. Clinvar id is 1988580.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK5	NM_004935.4	c.484-11del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000485972.6	NP_004926.1
CDK5	NM_001164410.3	c.388-11del		splice_polypyrimidine_tract_variant, intron_variant			NP_001157882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK5	ENST00000485972.6	c.484-11del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004935.4	ENSP00000419782	P1
CDK5	ENST00000297518.4	c.388-11del		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000297518
CDK5	ENST00000487703.5	n.848-11del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00260 AC: 393 AN: 151272 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00866

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00119

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000629

Gnomad FIN AF: 0.000380

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000885

Gnomad OTH AF: 0.00241

GnomAD3 exomes AF: 0.000904 AC: 221 AN: 244542 Hom.: 2 AF XY: 0.000722 AC XY: 96 AN XY: 132996

Gnomad AFR exome AF: 0.00910

Gnomad AMR exome AF: 0.000855

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000831

Gnomad FIN exome AF: 0.000561

Gnomad NFE exome AF: 0.000109

Gnomad OTH exome AF: 0.000842

GnomAD4 exome AF: 0.000403 AC: 585 AN: 1451424 Hom.: 6 Cov.: 30 AF XY: 0.000368 AC XY: 266 AN XY: 722430

Gnomad4 AFR exome AF: 0.00834

Gnomad4 AMR exome AF: 0.000829

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000825

Gnomad4 FIN exome AF: 0.000620

Gnomad4 NFE exome AF: 0.000101

Gnomad4 OTH exome AF: 0.000833

GnomAD4 genome AF: 0.00260 AC: 393 AN: 151388 Hom.: 3 Cov.: 33 AF XY: 0.00264 AC XY: 195 AN XY: 73934

Gnomad4 AFR AF: 0.00861

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000839

Gnomad4 FIN AF: 0.000380

Gnomad4 NFE AF: 0.0000885

Gnomad4 OTH AF: 0.00238

Alfa AF: 0.000365 Hom.: 0

Bravo AF: 0.00305

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3214589; hg19: chr7-150752470;