2-181548875-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_201548.5(CERKL):c.896-18T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 1,607,236 control chromosomes in the GnomAD database, including 284,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27014 hom., cov: 32)

Exomes 𝑓: 0.59 ( 257089 hom. )

Consequence

CERKL
NM_201548.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0370

Publications

8 publications found

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 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

CERKL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-181548875-A-T is Benign according to our data. Variant chr2-181548875-A-T is described in ClinVar as [Benign]. Clinvar id is 166846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERKL	NM_201548.5 link	c.896-18T>A		intron_variant	Intron 6 of 12	ENST00000410087.8	NP_963842.1	Q49MI3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERKL	ENST00000410087.8 link	c.896-18T>A		intron_variant	Intron 6 of 12	1	NM_201548.5	ENSP00000386725.3		Q49MI3-2

Frequencies

GnomAD3 genomes

AF:

0.593

AC:

90133

AN:

151896

Hom.:

26999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.613

Gnomad ASJ

AF:

0.609

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.830

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.575

Gnomad OTH

AF:

0.617

GnomAD2 exomes

AF:

0.611

AC:

152212

AN:

249028

AF XY:

0.623

show subpopulations

Gnomad AFR exome

AF:

0.601

Gnomad AMR exome

AF:

0.603

Gnomad ASJ exome

AF:

0.602

Gnomad EAS exome

AF:

0.634

Gnomad FIN exome

AF:

0.484

Gnomad NFE exome

AF:

0.576

Gnomad OTH exome

AF:

0.608

GnomAD4 exome

AF:

0.590

AC:

858167

AN:

1455222

Hom.:

257089

Cov.:

AF XY:

0.599

AC XY:

433683

AN XY:

724434

show subpopulations

African (AFR)

AF:

0.613

AC:

20440

AN:

33354

American (AMR)

AF:

0.604

AC:

26933

AN:

44604

Ashkenazi Jewish (ASJ)

AF:

0.611

AC:

15943

AN:

26084

East Asian (EAS)

AF:

0.617

AC:

24416

AN:

39590

South Asian (SAS)

AF:

0.836

AC:

72044

AN:

86128

European-Finnish (FIN)

AF:

0.488

AC:

26008

AN:

53258

Middle Eastern (MID)

AF:

0.720

AC:

4139

AN:

5752

European-Non Finnish (NFE)

AF:

0.571

AC:

632238

AN:

1106288

Other (OTH)

AF:

0.598

AC:

36006

AN:

60164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

16848

33696

50544

67392

84240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.593

AC:

90203

AN:

152014

Hom.:

27014

Cov.:

AF XY:

0.595

AC XY:

44232

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.608

AC:

25181

AN:

41448

American (AMR)

AF:

0.613

AC:

9363

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.609

AC:

2111

AN:

3466

East Asian (EAS)

AF:

0.635

AC:

3274

AN:

5158

South Asian (SAS)

AF:

0.830

AC:

4003

AN:

4822

European-Finnish (FIN)

AF:

0.505

AC:

5339

AN:

10564

Middle Eastern (MID)

AF:

0.663

AC:

195

AN:

294

European-Non Finnish (NFE)

AF:

0.575

AC:

39093

AN:

67972

Other (OTH)

AF:

0.614

AC:

1299

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1889

3778

5668

7557

9446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.587

Hom.:

4844

Bravo

AF:

0.596

Asia WGS

AF:

0.680

AC:

2365

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 26, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa 26

Benign:3

May 31, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

(source)

DANN

Benign

0.35

PhyloP100

0.037

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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2-181548875-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over