7-151055895-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004935.4(CDK5):​c.313-47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000852 in 1,174,002 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: CDK5 NM_004935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5	NM_004935.4	c.313-47G>A		intron_variant	Intron 5 of 11	ENST00000485972.6	NP_004926.1
CDK5	NM_001164410.3	c.313-289G>A		intron_variant	Intron 5 of 10		NP_001157882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5	ENST00000485972.6	c.313-47G>A		intron_variant	Intron 5 of 11	1	NM_004935.4	ENSP00000419782.1
CDK5	ENST00000297518.4	c.313-289G>A		intron_variant	Intron 5 of 10	1		ENSP00000297518.4
CDK5	ENST00000476691.1	n.466G>A		non_coding_transcript_exon_variant	Exon 1 of 2	4
CDK5	ENST00000487703.5	n.677-47G>A		intron_variant	Intron 5 of 7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.52e-7 AC: 1 AN: 1174002 Hom.: 0 Cov.: 16 AF XY: 0.00000169 AC XY: 1 AN XY: 590896

African (AFR) AF: 0.00 AC: 0 AN: 27606

American (AMR) AF: 0.00 AC: 0 AN: 37060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23868

East Asian (EAS) AF: 0.0000277 AC: 1 AN: 36090

South Asian (SAS) AF: 0.00 AC: 0 AN: 75482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 867616

Other (OTH) AF: 0.00 AC: 0 AN: 50916

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.80
PhyloP100		0.18

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;