rs745969938

Positions:

• chrX-18564526-GATATATATATAT-G
• chrX-18564526-GATATATATATAT-GATAT
• chrX-18564526-GATATATATATAT-GATATAT
• chrX-18564526-GATATATATATAT-GATATATAT
• chrX-18564526-GATATATATATAT-GATATATATAT
• chrX-18564526-GATATATATATAT-GATATATATATATAT
• chrX-18564526-GATATATATATAT-GATATATATATATATAT
• chrX-18564526-GATATATATATAT-GATATATATATATATATAT

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001323289.2(CDKL5):​c.145+17_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 0.000142 in 606,297 control chromosomes in the GnomAD database, including 3 homozygotes. There are 30 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000032 (0 hom., 2 hem., cov: 19)
  • Exomes 𝑓: 0.00016 (3 hom. 28 hem.)
• Consequence: CDKL5 NM_001323289.2 splice_donor_5th_base, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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 Benign. Variant got -12 ACMG points.

• BP6: Variant X-18564526-GATATATATATAT-G is Benign according to our data. Variant chrX-18564526-GATATATATATAT-G is described in ClinVar as [Likely_benign]. Clinvar id is 1292563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKL5	NM_001323289.2	c.145+17_145+28del		splice_donor_5th_base_variant, intron_variant		ENST00000623535.2	NP_001310218.1
CDKL5	NM_001037343.2	c.145+17_145+28del		splice_donor_5th_base_variant, intron_variant			NP_001032420.1
CDKL5	NM_003159.3	c.145+17_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+17_145+28del		splice_donor_5th_base_variant, intron_variant		1	NM_001323289.2	ENSP00000485244	P1

Frequencies

GnomAD3 genomes AF: 0.0000322 AC: 3 AN: 93263 Hom.: 0 Cov.: 19 AF XY: 0.0000855 AC XY: 2 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: 0.0000647

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000344 AC: 25 AN: 72668 Hom.: 1 AF XY: 0.00111 AC XY: 12 AN XY: 10808

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000977

Gnomad NFE exome AF: 0.000610

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000162 AC: 83 AN: 513034 Hom.: 3 AF XY: 0.000223 AC XY: 28 AN XY: 125428

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: 0.000452

Gnomad4 NFE exome AF: 0.000164

Gnomad4 OTH exome AF: 0.000466

GnomAD4 genome AF: 0.0000322 AC: 3 AN: 93263 Hom.: 0 Cov.: 19 AF XY: 0.0000855 AC XY: 2 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: 0.0000647

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 13, 2023

- -

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;