2-181549631-T-C

Position:

chr2-181549631-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_201548.5(CERKL):c.895+3A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,593,064 control chromosomes in the GnomAD database, including 13,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1568 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11573 hom. )

Consequence

CERKL
NM_201548.5 splice_donor_region, intron

Scores

Splicing: ADA: 0.9723

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 3.50

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 2-181549631-T-C is Benign according to our data. Variant chr2-181549631-T-C is described in ClinVar as [Benign]. Clinvar id is 257151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-181549631-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERKL	NM_201548.5 linkuse as main transcript	c.895+3A>G		splice_donor_region_variant, intron_variant		ENST00000410087.8	NP_963842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERKL	ENST00000410087.8 linkuse as main transcript	c.895+3A>G		splice_donor_region_variant, intron_variant		1	NM_201548.5	ENSP00000386725	P1	Q49MI3-2

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20928

AN:

152056

Hom.:

1566

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.0672

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.0602

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.138

AC:

34509

AN:

250700

Hom.:

2769

AF XY:

0.129

AC XY:

17489

AN XY:

135486

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.0664

Gnomad EAS exome

AF:

0.214

Gnomad SAS exome

AF:

0.0550

Gnomad FIN exome

AF:

0.211

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.120

AC:

172495

AN:

1440890

Hom.:

11573

Cov.:

AF XY:

0.117

AC XY:

83874

AN XY:

718166

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.207

Gnomad4 ASJ exome

AF:

0.0626

Gnomad4 EAS exome

AF:

0.222

Gnomad4 SAS exome

AF:

0.0531

Gnomad4 FIN exome

AF:

0.211

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.138

AC:

20954

AN:

152174

Hom.:

1568

Cov.:

AF XY:

0.143

AC XY:

10606

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.0672

Gnomad4 EAS

AF:

0.218

Gnomad4 SAS

AF:

0.0603

Gnomad4 FIN

AF:

0.200

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.121

Hom.:

553

Bravo

AF:

0.137

Asia WGS

AF:

0.169

AC:

586

AN:

3474

EpiCase

AF:

0.107

EpiControl

AF:

0.101

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 09, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Retinitis pigmentosa 26

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Benign

0.60

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over