2-181591267-C-T

Variant names:

• chr2-181591267-C-T
• rs993648
• NM_201548.5:c.481+12570G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201548.5(CERKL):​c.481+12570G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,776 control chromosomes in the GnomAD database, including 13,596 homozygotes. 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: 𝑓 0.37 (13596 hom., cov: 31)
• Consequence: CERKL NM_201548.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 15 publications found

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]

CERKL Gene-Disease associations (from GenCC):

• CERKL-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 26

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERKL	NM_201548.5	c.481+12570G>A		intron_variant	Intron 2 of 12	ENST00000410087.8	NP_963842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERKL	ENST00000410087.8	c.481+12570G>A		intron_variant	Intron 2 of 12	1	NM_201548.5	ENSP00000386725.3

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56032 AN: 151658 Hom.: 13565 Cov.: 31

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.0628

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.370 AC: 56123 AN: 151776 Hom.: 13596 Cov.: 31 AF XY: 0.374 AC XY: 27701 AN XY: 74118

African (AFR) AF: 0.684 AC: 28288 AN: 41386

American (AMR) AF: 0.364 AC: 5556 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3466

East Asian (EAS) AF: 0.373 AC: 1925 AN: 5166

South Asian (SAS) AF: 0.178 AC: 857 AN: 4812

European-Finnish (FIN) AF: 0.339 AC: 3546 AN: 10462

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14651 AN: 67926

Other (OTH) AF: 0.307 AC: 647 AN: 2110

Alfa AF: 0.269 Hom.: 22776

Bravo AF: 0.388

Asia WGS AF: 0.312 AC: 1085 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.29
PhyloP100		-0.042
Mutation Taster		=100/0	polymorphism (auto)

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: rs993648; hg19: chr2-182455994;