X-18442467-TTTTTGTTTTGTTTTG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001323289.2(CDKL5):c.-163+16803_-163+16817del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (9 hom., 135 hem., cov: 18)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: CDKL5 NM_001323289.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant X-18442467-TTTTTGTTTTGTTTTG-T is Benign according to our data. Variant chrX-18442467-TTTTTGTTTTGTTTTG-T is described in ClinVar as [Likely_benign]. Clinvar id is 1253979.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00653 (702/107483) while in subpopulation AFR AF= 0.0216 (630/29154). AF 95% confidence interval is 0.0202. There are 9 homozygotes in gnomad4. There are 135 alleles in male gnomad4 subpopulation. Median coverage is 18. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKL5	NM_001323289.2	c.-163+16803_-163+16817del		intron_variant		ENST00000623535.2
CDKL5	NM_001037343.2	c.-163+75_-163+89del		intron_variant
CDKL5	NM_003159.3	c.-163+16803_-163+16817del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKL5	ENST00000623535.2	c.-163+16803_-163+16817del		intron_variant		1	NM_001323289.2	P1

Frequencies

GnomAD3 genomes AF: 0.00650 AC: 698 AN: 107436 Hom.: 9 Cov.: 18 AF XY: 0.00430 AC XY: 132 AN XY: 30722

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00337

Gnomad ASJ AF: 0.000391

Gnomad EAS AF: 0.000584

Gnomad SAS AF: 0.00480

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00442

Gnomad NFE AF: 0.000290

Gnomad OTH AF: 0.00489

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: 0.00653 AC: 702 AN: 107483 Hom.: 9 Cov.: 18 AF XY: 0.00439 AC XY: 135 AN XY: 30781

Gnomad4 AFR AF: 0.0216

Gnomad4 AMR AF: 0.00336

Gnomad4 ASJ AF: 0.000391

Gnomad4 EAS AF: 0.000586

Gnomad4 SAS AF: 0.00482

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000290

Gnomad4 OTH AF: 0.00483

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 20, 2021

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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;