chrX-18442467-TTTTTG-T

Position:

• chrX-18442467-TTTTTG-T

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+16817delTTTTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 107,666 control chromosomes in the GnomAD database, including 107 homozygotes. There are 924 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.045 (107 hom., 923 hem., cov: 18)
  • Exomes 𝑓: 0.0045 (0 hom. 1 hem.)
• Consequence: CDKL5 NM_001323289.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.566

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-TTTTTG-T is Benign according to our data. Variant chrX-18442467-TTTTTG-T is described in ClinVar as [Benign]. Clinvar id is 1234180.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKL5	NM_001323289.2	c.-163+16813_-163+16817delTTTTG		intron_variant		ENST00000623535.2	NP_001310218.1
CDKL5	NM_001037343.2	c.-163+85_-163+89delTTTTG		intron_variant			NP_001032420.1
CDKL5	NM_003159.3	c.-163+16813_-163+16817delTTTTG		intron_variant			NP_003150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKL5	ENST00000623535.2	c.-163+16813_-163+16817delTTTTG		intron_variant		1	NM_001323289.2	ENSP00000485244.1

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 4835 AN: 107399 Hom.: 107 Cov.: 18 AF XY: 0.0301 AC XY: 923 AN XY: 30703

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.0828

Gnomad EAS AF: 0.0269

Gnomad SAS AF: 0.0524

Gnomad FIN AF: 0.0360

Gnomad MID AF: 0.0619

Gnomad NFE AF: 0.0567

Gnomad OTH AF: 0.0454

GnomAD4 exome AF: 0.00455 AC: 1 AN: 220 Hom.: 0 AF XY: 0.0100 AC XY: 1 AN XY: 100

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: 0.00559

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0450 AC: 4836 AN: 107446 Hom.: 107 Cov.: 18 AF XY: 0.0300 AC XY: 923 AN XY: 30762

Gnomad4 AFR AF: 0.0332

Gnomad4 AMR AF: 0.0214

Gnomad4 ASJ AF: 0.0828

Gnomad4 EAS AF: 0.0272

Gnomad4 SAS AF: 0.0526

Gnomad4 FIN AF: 0.0360

Gnomad4 NFE AF: 0.0567

Gnomad4 OTH AF: 0.0448

Bravo AF: 0.0479

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

Oct 08, 2019

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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;