chr1-150967418-T-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_022075.5(CERS2):āc.586A>Cā(p.Ser196Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000407 in 1,603,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00024 ( 0 hom., cov: 32)
Exomes š: 0.00042 ( 0 hom. )
Consequence
CERS2
NM_022075.5 missense
NM_022075.5 missense
Scores
3
3
10
Clinical Significance
Conservation
PhyloP100: 7.67
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.2975549).
BS2
High AC in GnomAd4 at 37 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CERS2 | NM_022075.5 | c.586A>C | p.Ser196Arg | missense_variant | 7/11 | ENST00000368954.10 | |
CERS2 | NM_181746.4 | c.586A>C | p.Ser196Arg | missense_variant | 7/11 | ||
CERS2 | XM_011509451.3 | c.646A>C | p.Ser216Arg | missense_variant | 7/11 | ||
CERS2 | XM_011509452.4 | c.586A>C | p.Ser196Arg | missense_variant | 7/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CERS2 | ENST00000368954.10 | c.586A>C | p.Ser196Arg | missense_variant | 7/11 | 1 | NM_022075.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000243 AC: 37AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000131 AC: 33AN: 251458Hom.: 1 AF XY: 0.000155 AC XY: 21AN XY: 135906
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GnomAD4 exome AF: 0.000425 AC: 616AN: 1450944Hom.: 0 Cov.: 30 AF XY: 0.000403 AC XY: 291AN XY: 722536
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GnomAD4 genome AF: 0.000243 AC: 37AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74472
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 28, 2024 | The c.586A>C (p.S196R) alteration is located in exon 7 (coding exon 6) of the CERS2 gene. This alteration results from a A to C substitution at nucleotide position 586, causing the serine (S) at amino acid position 196 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;.;T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N;N;.;N;N
Sift
Benign
T;T;T;.;T;T
Sift4G
Benign
T;T;T;.;.;.
Polyphen
0.095
.;B;B;.;.;.
Vest4
MutPred
0.78
.;Gain of MoRF binding (P = 0.02);Gain of MoRF binding (P = 0.02);Gain of MoRF binding (P = 0.02);Gain of MoRF binding (P = 0.02);Gain of MoRF binding (P = 0.02);
MVP
MPC
0.96
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at