rs60114040

Variant names:

• chrX-18442467-TTTTTGTTTTGTTTTGTTTTGTTTTG-T
• rs60114040
• NM_001323289.2:c.-163+16793_-163+16817delTTTTGTTTTGTTTTGTTTTGTTTTG

Your query was ambiguous. Multiple possible variants found:

• chrX-18442467-TTTTTGTTTTGTTTTGTTTTGTTTTG-T
• chrX-18442467-TTTTTGTTTTGTTTTGTTTTGTTTTG-TTTTTG
• chrX-18442467-TTTTTGTTTTGTTTTGTTTTGTTTTG-TTTTTGTTTTG
• chrX-18442467-TTTTTGTTTTGTTTTGTTTTGTTTTG-TTTTTGTTTTGTTTTG
• chrX-18442467-TTTTTGTTTTGTTTTGTTTTGTTTTG-TTTTTGTTTTGTTTTGTTTTG
• chrX-18442467-TTTTTGTTTTGTTTTGTTTTGTTTTG-TTTTTGTTTTGTTTTGTTTTGTTTTGTTTTG
• chrX-18442467-TTTTTGTTTTGTTTTGTTTTGTTTTG-TTTTTGTTTTGTTTTGTTTTGTTTTGTTTTGTTTTG
• chrX-18442467-TTTTTGTTTTGTTTTGTTTTGTTTTG-TTTTTGTTTTGTTTTGTTTTGTTTTGTTTTGTTTTGTTTTG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001323289.2(CDKL5):​c.-163+16793_-163+16817delTTTTGTTTTGTTTTGTTTTGTTTTG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0042 (4 hom., 105 hem., cov: 18)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: CDKL5 NM_001323289.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.942

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00423 (455/107482) while in subpopulation AFR AF= 0.0142 (414/29153). AF 95% confidence interval is 0.0131. There are 4 homozygotes in gnomad4. There are 105 alleles in male gnomad4 subpopulation. Median coverage is 18. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKL5	NM_001323289.2	c.-163+16793_-163+16817delTTTTGTTTTGTTTTGTTTTGTTTTG		intron_variant	Intron 1 of 17	ENST00000623535.2	NP_001310218.1
CDKL5	NM_001037343.2	c.-163+65_-163+89delTTTTGTTTTGTTTTGTTTTGTTTTG		intron_variant	Intron 2 of 21		NP_001032420.1
CDKL5	NM_003159.3	c.-163+16793_-163+16817delTTTTGTTTTGTTTTGTTTTGTTTTG		intron_variant	Intron 1 of 20		NP_003150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKL5	ENST00000623535.2	c.-163+16773_-163+16797delTTTTGTTTTGTTTTGTTTTGTTTTG		intron_variant	Intron 1 of 17	1	NM_001323289.2	ENSP00000485244.1

Frequencies

GnomAD3 genomes AF: 0.00424 AC: 455 AN: 107435 Hom.: 4 Cov.: 18 AF XY: 0.00345 AC XY: 106 AN XY: 30721

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00337

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: 0.0000193

Gnomad OTH AF: 0.00419

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 223 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 103

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00423 AC: 455 AN: 107482 Hom.: 4 Cov.: 18 AF XY: 0.00341 AC XY: 105 AN XY: 30780

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.00336

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000193

Gnomad4 OTH AF: 0.00414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60114040; hg19: chrX-18460587;