Variant 1-150966805-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022075.5(CERS2):c.799G>A(p.Val267Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00557 in 1,614,048 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 30 hom. )

Consequence

CERS2
NM_022075.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.256

Variant links:

Genes affected

CERS2 (HGNC:14076): (ceramide synthase 2) This gene encodes a protein that has sequence similarity to yeast longevity assurance gene 1. Mutation or overexpression of the related gene in yeast has been shown to alter yeast lifespan. The human protein may play a role in the regulation of cell growth. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

CERS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009523839).

BP6

Variant 1-150966805-C-T is Benign according to our data. Variant chr1-150966805-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639166.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 617 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CERS2	NM_022075.5 linkuse as main transcript	c.799G>A	p.Val267Ile	missense_variant	9/11	ENST00000368954.10
CERS2	NM_181746.4 linkuse as main transcript	c.799G>A	p.Val267Ile	missense_variant	9/11
CERS2	XM_011509451.3 linkuse as main transcript	c.859G>A	p.Val287Ile	missense_variant	9/11
CERS2	XM_011509452.4 linkuse as main transcript	c.799G>A	p.Val267Ile	missense_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS2	ENST00000368954.10 linkuse as main transcript	c.799G>A	p.Val267Ile	missense_variant	9/11	1	NM_022075.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

617

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00269

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00866

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00617

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00435

AC:

1093

AN:

251478

Hom.:

AF XY:

0.00419

AC XY:

569

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.00919

Gnomad NFE exome

AF:

0.00654

Gnomad OTH exome

AF:

0.00570

GnomAD4 exome

AF:

0.00573

AC:

8369

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00559

AC XY:

4067

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.000651

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000812

Gnomad4 FIN exome

AF:

0.00870

Gnomad4 NFE exome

AF:

0.00658

Gnomad4 OTH exome

AF:

0.00565

GnomAD4 genome

AF:

0.00405

AC:

617

AN:

152230

Hom.:

Cov.:

AF XY:

0.00417

AC XY:

310

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000988

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00866

Gnomad4 NFE

AF:

0.00618

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00589

Hom.:

Bravo

AF:

0.00414

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00744

AC:

ExAC

AF:

0.00440

AC:

534

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00453

EpiControl

AF:

0.00533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

CERS2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

Cadd

Benign

2.8

Dann

Benign

0.86

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.68

T;T;.;T

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.0095

T;T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

0.51

D;D;D;D

PrimateAI

Benign

0.34

PROVEAN

Benign

0.40

N;N;N;.

Sift

Benign

1.0

T;T;T;.

Sift4G

Benign

1.0

T;T;T;.

Polyphen

0.082

.;B;B;.

Vest4

0.10

MVP

0.51

MPC

0.47

ClinPred

0.0047

GERP RS

-0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.027

gMVP

0.38

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