7-151054979-T-C

Variant names:

• chr7-151054979-T-C
• rs891507
• NM_004935.4:c.650+48A>G

Variant summary

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

The NM_004935.4(CDK5):​c.650+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,589,312 control chromosomes in the GnomAD database, including 584,574 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 0.88 (59517 hom., cov: 31)
  • Exomes 𝑓: 0.85 (525057 hom.)
• Consequence: CDK5 NM_004935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.47
• Publications: 17 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 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.650+48A>G		intron	N/A	NP_004926.1	A0A090N7W4
	CDK5	NM_001164410.3		c.554+48A>G		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.650+48A>G		intron	N/A	ENSP00000419782.1	Q00535-1
	CDK5	ENST00000297518.4	TSL:1	c.554+48A>G		intron	N/A	ENSP00000297518.4	Q00535-2
	CDK5	ENST00000891064.1		c.686+48A>G		intron	N/A	ENSP00000561123.1

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134353 AN: 152090 Hom.: 59460 Cov.: 31

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.883

GnomAD2 exomes AF: 0.876 AC: 215506 AN: 245886 AF XY: 0.870

Gnomad AFR exome AF: 0.945

Gnomad AMR exome AF: 0.934

Gnomad ASJ exome AF: 0.901

Gnomad EAS exome AF: 0.958

Gnomad FIN exome AF: 0.866

Gnomad NFE exome AF: 0.843

Gnomad OTH exome AF: 0.874

GnomAD4 exome AF: 0.854 AC: 1227323 AN: 1437104 Hom.: 525057 Cov.: 25 AF XY: 0.853 AC XY: 611160 AN XY: 716274

African (AFR) AF: 0.943 AC: 31150 AN: 33018

American (AMR) AF: 0.931 AC: 41383 AN: 44442

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 23353 AN: 25936

East Asian (EAS) AF: 0.972 AC: 38433 AN: 39546

South Asian (SAS) AF: 0.851 AC: 72808 AN: 85512

European-Finnish (FIN) AF: 0.864 AC: 45873 AN: 53078

Middle Eastern (MID) AF: 0.874 AC: 5008 AN: 5732

European-Non Finnish (NFE) AF: 0.842 AC: 917748 AN: 1090318

Other (OTH) AF: 0.866 AC: 51567 AN: 59522

GnomAD4 genome AF: 0.883 AC: 134469 AN: 152208 Hom.: 59517 Cov.: 31 AF XY: 0.883 AC XY: 65732 AN XY: 74406

African (AFR) AF: 0.940 AC: 39034 AN: 41540

American (AMR) AF: 0.900 AC: 13768 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3148 AN: 3472

East Asian (EAS) AF: 0.956 AC: 4938 AN: 5166

South Asian (SAS) AF: 0.843 AC: 4065 AN: 4822

European-Finnish (FIN) AF: 0.863 AC: 9147 AN: 10596

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57455 AN: 68002

Other (OTH) AF: 0.885 AC: 1869 AN: 2112

Alfa AF: 0.877 Hom.: 24285

Bravo AF: 0.891

Asia WGS AF: 0.914 AC: 3178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0090
DANN	Benign	0.19
PhyloP100		-6.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs891507; hg19: chr7-150752066;