NM_001323289.2:c.283-99C>T

Variant names:

• chrX-18579749-C-T
• rs4825261
• NM_001323289.2:c.283-99C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001323289.2(CDKL5):​c.283-99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 783,246 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 29 hemizygotes in GnomAD. 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 0.00023 (0 hom., 9 hem., cov: 23)
  • Exomes 𝑓: 0.00011 (0 hom. 20 hem.)
• Consequence: CDKL5 NM_001323289.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739

Genes affected

CDKL5 (HGNC:11411): (cyclin dependent kinase like 5) This gene is a member of Ser/Thr protein kinase family and encodes a phosphorylated protein with protein kinase activity. Mutations in this gene have been associated with X-linked infantile spasm syndrome (ISSX), also known as X-linked West syndrome, and Rett syndrome (RTT). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000227 (25/110156) while in subpopulation AMR AF= 0.00165 (17/10321). AF 95% confidence interval is 0.00105. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKL5	NM_001323289.2	c.283-99C>T		intron_variant	Intron 5 of 17	ENST00000623535.2	NP_001310218.1
CDKL5	NM_001037343.2	c.283-99C>T		intron_variant	Intron 6 of 21		NP_001032420.1
CDKL5	NM_003159.3	c.283-99C>T		intron_variant	Intron 5 of 20		NP_003150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKL5	ENST00000623535.2	c.283-99C>T		intron_variant	Intron 5 of 17	1	NM_001323289.2	ENSP00000485244.1

Frequencies

GnomAD3 genomes AF: 0.000227 AC: 25 AN: 110105 Hom.: 0 Cov.: 23 AF XY: 0.000278 AC XY: 9 AN XY: 32421

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00165

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000111 AC: 75 AN: 673090 Hom.: 0 AF XY: 0.000109 AC XY: 20 AN XY: 183842

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000539

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000252

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000105

Gnomad4 OTH exome AF: 0.000192

GnomAD4 genome AF: 0.000227 AC: 25 AN: 110156 Hom.: 0 Cov.: 23 AF XY: 0.000277 AC XY: 9 AN XY: 32480

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00165

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000152

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.088
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4825261; hg19: chrX-18597869;