2-181590050-G-T

Variant names:

• chr2-181590050-G-T
• rs1441162
• NM_201548.5:c.481+13787C>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+13787C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,514 control chromosomes in the GnomAD database, including 7,555 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 0.23 (7555 hom., cov: 31)
• Consequence: CERKL NM_201548.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.996
• Publications: 2 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201548.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERKL	NM_201548.5	MANE Select	c.481+13787C>A		intron	N/A	NP_963842.1
	CERKL	NM_001030311.3		c.481+13787C>A		intron	N/A	NP_001025482.1
	CERKL	NM_001160277.2		c.481+13787C>A		intron	N/A	NP_001153749.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERKL	ENST00000410087.8	TSL:1 MANE Select	c.481+13787C>A		intron	N/A	ENSP00000386725.3
	CERKL	ENST00000339098.9	TSL:1	c.481+13787C>A		intron	N/A	ENSP00000341159.5
	CERKL	ENST00000374970.6	TSL:1	c.481+13787C>A		intron	N/A	ENSP00000364109.2

Frequencies

GnomAD3 genomes AF: 0.231 AC: 34976 AN: 151398 Hom.: 7537 Cov.: 31

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0799

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.231 AC: 35039 AN: 151514 Hom.: 7555 Cov.: 31 AF XY: 0.230 AC XY: 17044 AN XY: 74040

African (AFR) AF: 0.573 AC: 23597 AN: 41178

American (AMR) AF: 0.187 AC: 2854 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 276 AN: 3460

East Asian (EAS) AF: 0.119 AC: 612 AN: 5146

South Asian (SAS) AF: 0.114 AC: 547 AN: 4786

European-Finnish (FIN) AF: 0.120 AC: 1262 AN: 10510

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0799 AC: 5425 AN: 67898

Other (OTH) AF: 0.189 AC: 397 AN: 2100

Alfa AF: 0.185 Hom.: 824

Bravo AF: 0.254

Asia WGS AF: 0.130 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.31
PhyloP100		-1.0
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: rs1441162; hg19: chr2-182454777;