X-18564526-GATATATATATAT-GATAT

Position:

• chrX-18564526-GATATATATATAT-GATAT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001323289.2(CDKL5):​c.145+21_145+28del variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000363 in 606,181 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000011 (0 hom., 0 hem., cov: 19)
  • Exomes 𝑓: 0.000041 (0 hom. 1 hem.)
• Consequence: CDKL5 NM_001323289.2 splice_donor_5th_base, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.26

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 -2 ACMG points.

• BP6: Variant X-18564526-GATATATAT-G is Benign according to our data. Variant chrX-18564526-GATATATAT-G is described in ClinVar as [Likely_benign]. Clinvar id is 2928790.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKL5	NM_001323289.2	c.145+21_145+28del		splice_donor_5th_base_variant, intron_variant		ENST00000623535.2	NP_001310218.1
CDKL5	NM_001037343.2	c.145+21_145+28del		splice_donor_5th_base_variant, intron_variant			NP_001032420.1
CDKL5	NM_003159.3	c.145+21_145+28del		splice_donor_5th_base_variant, intron_variant			NP_003150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKL5	ENST00000623535.2	c.145+21_145+28del		splice_donor_5th_base_variant, intron_variant		1	NM_001323289.2	ENSP00000485244	P1

Frequencies

GnomAD3 genomes AF: 0.0000107 AC: 1 AN: 93263 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 23405

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000216

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000409 AC: 21 AN: 512918 Hom.: 0 AF XY: 0.00000798 AC XY: 1 AN XY: 125364

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000819

Gnomad4 EAS exome AF: 0.0000519

Gnomad4 SAS exome AF: 0.0000343

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000389

Gnomad4 OTH exome AF: 0.000169

GnomAD4 genome AF: 0.0000107 AC: 1 AN: 93263 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 23405

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000216

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 2;CN128785:Angelman syndrome-like Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 10, 2023

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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: rs745969938; hg19: chrX-18582646;