2-181539124-G-T

Position:

• chr2-181539124-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_201548.5(CERKL):​c.1506C>A​(p.Asp502Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D502D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CERKL NM_201548.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.749

Genes affected

CERKL (HGNC:21699): (ceramide kinase like) This gene was initially identified as a locus (RP26) associated with an autosomal recessive form of retinitis pigmentosa (arRP) disease. This gene encodes a protein with ceramide kinase-like domains, however, the protein does not phosphorylate ceramide and its target substrate is currently unknown. This protein may be a negative regulator of apoptosis in photoreceptor cells. Mutations in this gene cause a form of retinitis pigmentosa characterized by autosomal recessive cone and rod dystrophy (arCRD). Alternative splicing of this gene results in multiple transcript variants encoding different isoforms and non-coding transcripts.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17434138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERKL	NM_201548.5	c.1506C>A	p.Asp502Glu	missense_variant	12/13	ENST00000410087.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERKL	ENST00000410087.8	c.1506C>A	p.Asp502Glu	missense_variant	12/13	1	NM_201548.5	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.82
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.85	T;D;D;T;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.98	D;D;D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.5	N;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	0.37	T;T;T;T;T
Polyphen		0.77	P;.;P;P;P
Vest4		0.33
MutPred		0.73		.;.;.;Loss of sheet (P = 0.0457);.;
MVP		0.23
MPC		0.18
ClinPred		0.45	T
GERP RS		0.14
Varity_R		0.072
gMVP		0.26

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: rs10180793; hg19: chr2-182403851;