X-18442467-T-TTTTTG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001323289.2(CDKL5):c.-163+16813_-163+16817dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (380 hom., 1461 hem., cov: 18)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: CDKL5 NM_001323289.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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-T-TTTTTG is Benign according to our data. Variant chrX-18442467-T-TTTTTG is described in ClinVar as [Benign]. Clinvar id is 1258365.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKL5	NM_001323289.2	c.-163+16813_-163+16817dup		intron_variant		ENST00000623535.2
CDKL5	NM_001037343.2	c.-163+85_-163+89dup		intron_variant
CDKL5	NM_003159.3	c.-163+16813_-163+16817dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKL5	ENST00000623535.2	c.-163+16813_-163+16817dup		intron_variant		1	NM_001323289.2	P1

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 8430 AN: 107365 Hom.: 381 Cov.: 18 AF XY: 0.0475 AC XY: 1458 AN XY: 30669

Gnomad AFR AF: 0.0968

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0470

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.0514

Gnomad MID AF: 0.0885

Gnomad NFE AF: 0.0781

Gnomad OTH AF: 0.0908

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 222 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 102

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: 0.0785 AC: 8430 AN: 107412 Hom.: 380 Cov.: 18 AF XY: 0.0475 AC XY: 1461 AN XY: 30728

Gnomad4 AFR AF: 0.0968

Gnomad4 AMR AF: 0.0466

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0472

Gnomad4 SAS AF: 0.0333

Gnomad4 FIN AF: 0.0514

Gnomad4 NFE AF: 0.0781

Gnomad4 OTH AF: 0.0903

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 16, 2020

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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;