chrX-18608991-G-A

Position:

• chrX-18608991-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001323289.2(CDKL5):​c.2046+79G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00937 in 672,225 control chromosomes in the GnomAD database, including 93 homozygotes. There are 1,789 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.021 (50 hom., 657 hem., cov: 22)
  • Exomes 𝑓: 0.0069 (43 hom. 1132 hem.)
• Consequence: CDKL5 NM_001323289.2 intron
• Clinical Significance: Benign no assertion criteria provided B:1 O:1
• Conservation: PhyloP100: -3.65

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant X-18608991-G-A is Benign according to our data. Variant chrX-18608991-G-A is described in ClinVar as [Benign]. Clinvar id is 156076.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-18608991-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKL5	NM_001323289.2	c.2046+79G>A		intron_variant		ENST00000623535.2
CDKL5	NM_001037343.2	c.2046+79G>A		intron_variant
CDKL5	NM_003159.3	c.2046+79G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKL5	ENST00000623535.2	c.2046+79G>A		intron_variant		1	NM_001323289.2	P1

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 2404 AN: 112034 Hom.: 50 Cov.: 22 AF XY: 0.0192 AC XY: 656 AN XY: 34246

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00934

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00444

Gnomad FIN AF: 0.00347

Gnomad MID AF: 0.0504

Gnomad NFE AF: 0.00483

Gnomad OTH AF: 0.0192

GnomAD4 exome AF: 0.00695 AC: 3891 AN: 560138 Hom.: 43 AF XY: 0.00683 AC XY: 1132 AN XY: 165712

Gnomad4 AFR exome AF: 0.0584

Gnomad4 AMR exome AF: 0.00703

Gnomad4 ASJ exome AF: 0.0283

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00182

Gnomad4 FIN exome AF: 0.00393

Gnomad4 NFE exome AF: 0.00473

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.0215 AC: 2406 AN: 112087 Hom.: 50 Cov.: 22 AF XY: 0.0191 AC XY: 657 AN XY: 34309

Gnomad4 AFR AF: 0.0616

Gnomad4 AMR AF: 0.00933

Gnomad4 ASJ AF: 0.0302

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00445

Gnomad4 FIN AF: 0.00347

Gnomad4 NFE AF: 0.00479

Gnomad4 OTH AF: 0.0190

Alfa AF: 0.0143 Hom.: 57

Bravo AF: 0.0240

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

not specified Benign:1

Benign, no assertion criteria provided

curation

RettBASE

Mar 13, 2014

- -

not provided Other:1

not provided, flagged submission

literature only

RettBASE

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0030
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs147819758; hg19: chrX-18627111;