chr1-150966264-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022075.5(CERS2):c.1027C>G(p.Arg343Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CERS2
NM_022075.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.99

Publications

0 publications found

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:

ENSG00000259357 (HGNC:58295):

ENSG00000259357 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16539636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS2	NM_022075.5 link	c.1027C>G	p.Arg343Gly	missense_variant	Exon 11 of 11	ENST00000368954.10	NP_071358.1	Q96G23
CERS2	NM_181746.4 link	c.1027C>G	p.Arg343Gly	missense_variant	Exon 11 of 11		NP_859530.1	Q96G23
CERS2	XM_011509451.3 link	c.1087C>G	p.Arg363Gly	missense_variant	Exon 11 of 11		XP_011507753.1
CERS2	XM_011509452.4 link	c.1027C>G	p.Arg343Gly	missense_variant	Exon 11 of 11		XP_011507754.1	Q96G23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS2	ENST00000368954.10 link	c.1027C>G	p.Arg343Gly	missense_variant	Exon 11 of 11	1	NM_022075.5	ENSP00000357950.5		Q96G23

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725878

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33236

American (AMR)

AF:

0.00

AC:

AN:

43612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26028

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

85814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111148

Other (OTH)

AF:

0.00

AC:

AN:

60276

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1027C>G (p.R343G) alteration is located in exon 11 (coding exon 10) of the CERS2 gene. This alteration results from a C to G substitution at nucleotide position 1027, causing the arginine (R) at amino acid position 343 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.033

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.94

D;.

M_CAP

Benign

0.0053

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

PhyloP100

3.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.043

Sift

Benign

0.37

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.18

B;B

Vest4

0.32

MutPred

0.23

Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);

MVP

0.21

MPC

0.94

ClinPred

0.22

GERP RS

3.6

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.11

gMVP

0.39

Mutation Taster

=64/36

polymorphism

(source)

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

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chr1-150966264-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over