rs1295816474

Variant names:

• chr14-50395843-T-G
• rs1295816474
• NM_004196.7:c.26A>C

Your query was ambiguous. Multiple possible variants found:

• chr14-50395843-T-G
• chr14-50395843-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004196.7(CDKL1):​c.26A>C​(p.Lys9Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CDKL1 NM_004196.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.26
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30008402).

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.26A>C	p.Lys9Thr	missense	Exon 2 of 10	NP_004187.3
	CDKL1	NM_001423761.1		c.26A>C	p.Lys9Thr	missense	Exon 1 of 9	NP_001410690.1	Q00532-1
	CDKL1	NM_001423762.1		c.26A>C	p.Lys9Thr	missense	Exon 2 of 10	NP_001410691.1	A0A9S7JKS7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL1	ENST00000395834.6	TSL:1 MANE Select	c.26A>C	p.Lys9Thr	missense	Exon 2 of 10	ENSP00000379176.2	A0A9S7JKS7
	CDKL1	ENST00000216378.2	TSL:1	c.29A>C	p.Lys10Thr	missense	Exon 2 of 9	ENSP00000216378.2	A0A5H1ZRP5
	CDKL1	ENST00000356146.5	TSL:1	n.596A>C		non_coding_transcript_exon	Exon 5 of 20

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251358 AF XY: 0.00000736

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459680 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 726326

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000541 AC: 6 AN: 1109988

Other (OTH) AF: 0.00 AC: 0 AN: 60314

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	27
DANN	Uncertain	0.99
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.47	T
PhyloP100		2.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.38
Sift	Benign	0.24	T
Sift4G	Benign	0.35	T
Vest4		0.42
MVP		0.44
MPC		0.40
ClinPred		0.90	D
GERP RS		4.3
gMVP		0.43
Mutation Taster		=12/88	disease causing

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

Other links and lift over

dbSNP: rs1295816474; hg19: chr14-50862561;