1-155268052-T-G

Variant names:

• chr1-155268052-T-G
• rs1310022416
• NM_001294338.2:c.629A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001294338.2(CLK2):​c.629A>C​(p.Asn210Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N210S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLK2 NM_001294338.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02
• Publications: 4 publications found

Genes affected

CLK2 (HGNC:2069): (CDC like kinase 2) This gene encodes a dual specificity protein kinase that phosphorylates serine/threonine and tyrosine-containing substrates. Activity of this protein regulates serine- and arginine-rich (SR) proteins of the spliceosomal complex, thereby influencing alternative transcript splicing. Chromosomal translocations have been characterized between this locus and the PAFAH1B3 (platelet-activating factor acetylhydrolase 1b, catalytic subunit 3 (29kDa)) gene on chromosome 19, resulting in the production of a fusion protein. Note that this gene is distinct from the TELO2 gene (GeneID:9894), which shares the CLK2 alias, but encodes a protein that is involved in telomere length regulation. There is a pseudogene for this gene on chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001294338.2. 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
	CLK2	NM_001294338.2	MANE Select	c.629A>C	p.Asn210Thr	missense	Exon 6 of 13	NP_001281267.1	P49760-1
	CLK2	NM_003993.4		c.626A>C	p.Asn209Thr	missense	Exon 6 of 13	NP_003984.2
	CLK2	NM_001363704.2		c.623A>C	p.Asn208Thr	missense	Exon 6 of 13	NP_001350633.1	B1AVT0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLK2	ENST00000368361.9	TSL:1 MANE Select	c.629A>C	p.Asn210Thr	missense	Exon 6 of 13	ENSP00000357345.4	P49760-1
	CLK2	ENST00000361168.9	TSL:1	c.626A>C	p.Asn209Thr	missense	Exon 6 of 13	ENSP00000354856.5	P49760-3
	CLK2	ENST00000476983.5	TSL:1	n.670A>C		non_coding_transcript_exon	Exon 5 of 12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.65	N
PhyloP100		8.0
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.033	D
Polyphen		0.83	P
Vest4		0.73
MutPred		0.48		Loss of stability (P = 0.0631)
MVP		0.56
MPC		2.4
ClinPred		0.93	D
GERP RS		5.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.72
gMVP		0.65
Mutation Taster		=39/61	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: rs1310022416; hg19: chr1-155237843;