chrX-18524039-C-T

Position:

• chrX-18524039-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001323289.2(CDKL5):​c.99+13185C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.82 (26587 hom., 26629 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: CDKL5 NM_001323289.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKL5	NM_001323289.2	c.99+13185C>T		intron_variant		ENST00000623535.2	NP_001310218.1
CDKL5	NM_001037343.2	c.99+13185C>T		intron_variant			NP_001032420.1
CDKL5	NM_003159.3	c.99+13185C>T		intron_variant			NP_003150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKL5	ENST00000623535.2	c.99+13185C>T		intron_variant		1	NM_001323289.2	ENSP00000485244.1

Frequencies

GnomAD3 genomes AF: 0.821 AC: 90579 AN: 110342 Hom.: 26586 Cov.: 22 AF XY: 0.817 AC XY: 26571 AN XY: 32518

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.832

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.821 AC: 90634 AN: 110394 Hom.: 26587 Cov.: 22 AF XY: 0.817 AC XY: 26629 AN XY: 32580

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.816

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.834

Alfa AF: 0.776 Hom.: 56733

Bravo AF: 0.838

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.72

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: rs5909187; hg19: chrX-18542159;