chr7-151055109-CAG-C

Position:

• chr7-151055109-CAG-C

Variant summary

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

The NM_004935.4(CDK5):​c.581-15_581-14del 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 0.000346 in 1,608,596 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00036 (2 hom.)
• Consequence: CDK5 NM_004935.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0840

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 7-151055109-CAG-C is Benign according to our data. Variant chr7-151055109-CAG-C is described in ClinVar as [Benign]. Clinvar id is 1991822.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK5	NM_004935.4	c.581-15_581-14del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000485972.6	NP_004926.1
CDK5	NM_001164410.3	c.485-15_485-14del		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.581-15_581-14del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004935.4	ENSP00000419782	P1
CDK5	ENST00000297518.4	c.485-15_485-14del		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000297518

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000346 AC: 84 AN: 242836 Hom.: 1 AF XY: 0.000449 AC XY: 59 AN XY: 131516

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.000412

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000335

Gnomad SAS exome AF: 0.00127

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000209

Gnomad OTH exome AF: 0.000341

GnomAD4 exome AF: 0.000361 AC: 525 AN: 1456244 Hom.: 2 AF XY: 0.000389 AC XY: 282 AN XY: 724038

Gnomad4 AFR exome AF: 0.0000898

Gnomad4 AMR exome AF: 0.000361

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00255

Gnomad4 SAS exome AF: 0.00136

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000234

Gnomad4 OTH exome AF: 0.000299

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152352 Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15 AN XY: 74510

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000145 Hom.: 0

Bravo AF: 0.000219

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 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3214588; hg19: chr7-150752196;