chr14-100149539-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_206918.3(DEGS2):c.254C>T(p.Thr85Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,605,000 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 35)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
DEGS2
NM_206918.3 missense
NM_206918.3 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 9.85
Genes affected
DEGS2 (HGNC:20113): (delta 4-desaturase, sphingolipid 2) This gene encodes a bifunctional enzyme that is involved in the biosynthesis of phytosphingolipids in human skin and in other phytosphingolipid-containing tissues. This enzyme can act as a sphingolipid delta(4)-desaturase, and also as a sphingolipid C4-hydroxylase. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEGS2 | NM_206918.3 | c.254C>T | p.Thr85Met | missense_variant | 2/3 | ENST00000305631.7 | |
DEGS2 | XM_006720043.4 | c.146C>T | p.Thr49Met | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEGS2 | ENST00000305631.7 | c.254C>T | p.Thr85Met | missense_variant | 2/3 | 1 | NM_206918.3 | P1 | |
DEGS2 | ENST00000553834.1 | c.83-2632C>T | intron_variant | 3 | |||||
DEGS2 | ENST00000557117.1 | n.286C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152226Hom.: 0 Cov.: 35
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000519 AC: 12AN: 231106Hom.: 0 AF XY: 0.0000237 AC XY: 3AN XY: 126698
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GnomAD4 exome AF: 0.0000158 AC: 23AN: 1452774Hom.: 0 Cov.: 38 AF XY: 0.00000830 AC XY: 6AN XY: 722522
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152226Hom.: 0 Cov.: 35 AF XY: 0.0000269 AC XY: 2AN XY: 74366
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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 | Dec 14, 2023 | The c.254C>T (p.T85M) alteration is located in exon 2 (coding exon 2) of the DEGS2 gene. This alteration results from a C to T substitution at nucleotide position 254, causing the threonine (T) at amino acid position 85 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
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