chr2-181539124-G-A

Position:

chr2-181539124-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000410087.8(CERKL):c.1506C>T(p.Asp502=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,608,470 control chromosomes in the GnomAD database, including 801,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 75051 hom., cov: 31)

Exomes 𝑓: 1.0 ( 726860 hom. )

Consequence

CERKL
ENST00000410087.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.749

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 2-181539124-G-A is Benign according to our data. Variant chr2-181539124-G-A is described in ClinVar as [Benign]. Clinvar id is 166844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-181539124-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.749 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.994 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.1506C>T	p.Asp502=	synonymous_variant	12/13	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.1506C>T	p.Asp502=	synonymous_variant	12/13	1	NM_201548.5	ENSP00000386725	P1	Q49MI3-2

Frequencies

GnomAD3 genomes

AF:

0.993

AC:

151050

AN:

152134

Hom.:

75001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.976

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.995

Gnomad ASJ

AF:

0.996

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.995

GnomAD3 exomes

AF:

0.998

AC:

250751

AN:

251272

Hom.:

125119

AF XY:

0.998

AC XY:

135604

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.976

Gnomad AMR exome

AF:

0.998

Gnomad ASJ exome

AF:

0.995

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.999

GnomAD4 exome

AF:

0.999

AC:

1454956

AN:

1456218

Hom.:

726860

Cov.:

AF XY:

0.999

AC XY:

724216

AN XY:

724762

show subpopulations

Gnomad4 AFR exome

AF:

0.976

Gnomad4 AMR exome

AF:

0.998

Gnomad4 ASJ exome

AF:

0.996

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.997

GnomAD4 genome

AF:

0.993

AC:

151159

AN:

152252

Hom.:

75051

Cov.:

AF XY:

0.993

AC XY:

73902

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.976

Gnomad4 AMR

AF:

0.995

Gnomad4 ASJ

AF:

0.996

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.995

Alfa

AF:

0.998

Hom.:

109720

Bravo

AF:

0.992

Asia WGS

AF:

0.997

AC:

3464

AN:

3476

EpiCase

AF:

1.00

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 19, 2014	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
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 26

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 21, 2019	- -

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

-0.55

CADD

Benign

5.0

DANN

Benign

0.76

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

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