14-50342977-G-C

Variant names:

• chr14-50342977-G-C
• rs11570829
• NM_004196.7:c.364-755C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004196.7(CDKL1):​c.364-755C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000083 in 1,204,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: CDKL1 NM_004196.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 0 publications found

Genes affected

CDKL1 (HGNC:1781): (cyclin dependent kinase like 1) This gene product is a member of a large family of CDC2-related serine/threonine protein kinases that accumulates primarily in the nucleus. [provided by RefSeq, Nov 2018]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004196.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL1	NM_004196.7	MANE Select	c.364-755C>G		intron	N/A	NP_004187.3
	CDKL1	NM_001423761.1		c.364-755C>G		intron	N/A	NP_001410690.1
	CDKL1	NM_001423762.1		c.364-755C>G		intron	N/A	NP_001410691.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL1	ENST00000395834.6	TSL:1 MANE Select	c.364-755C>G		intron	N/A	ENSP00000379176.2
	CDKL1	ENST00000216378.2	TSL:1	c.367-755C>G		intron	N/A	ENSP00000216378.2
	CDKL1	ENST00000356146.5	TSL:1	n.2308C>G		non_coding_transcript_exon	Exon 16 of 20

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.30e-7 AC: 1 AN: 1204210 Hom.: 0 Cov.: 30 AF XY: 0.00000168 AC XY: 1 AN XY: 595710

African (AFR) AF: 0.00 AC: 0 AN: 25956

American (AMR) AF: 0.00 AC: 0 AN: 35936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16574

East Asian (EAS) AF: 0.00 AC: 0 AN: 16270

South Asian (SAS) AF: 0.00 AC: 0 AN: 81210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30844

Middle Eastern (MID) AF: 0.000224 AC: 1 AN: 4464

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 949314

Other (OTH) AF: 0.00 AC: 0 AN: 43642

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.15
DANN	Benign	0.60
PhyloP100		-2.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11570829; hg19: chr14-50809695;