Variant chr14-100159551-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000305631.7(DEGS2):c.37G>T(p.Val13Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000354 in 1,356,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

DEGS2
ENST00000305631.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.05

Variant links:

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]

DEGS2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEGS2	NM_206918.3 linkuse as main transcript	c.37G>T	p.Val13Phe	missense_variant	1/3	ENST00000305631.7	NP_996801.2
DEGS2	XM_006720043.4 linkuse as main transcript	c.-27+7054G>T		intron_variant			XP_006720106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEGS2	ENST00000305631.7 linkuse as main transcript	c.37G>T	p.Val13Phe	missense_variant	1/3	1	NM_206918.3	ENSP00000307126	P1
DEGS2	ENST00000553834.1 linkuse as main transcript	c.37G>T	p.Val13Phe	missense_variant	1/2	3		ENSP00000450637

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000186

AC:

AN:

107590

Hom.:

AF XY:

0.0000340

AC XY:

AN XY:

58874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000512

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000354

AC:

AN:

1356606

Hom.:

Cov.:

AF XY:

0.0000389

AC XY:

AN XY:

669006

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.0000709

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.00000378

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 29, 2024

The c.37G>T (p.V13F) alteration is located in exon 1 (coding exon 1) of the DEGS2 gene. This alteration results from a G to T substitution at nucleotide position 37, causing the valine (V) at amino acid position 13 to be replaced by a phenylalanine (F). 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

Uncertain

0.38

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

T;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;D

M_CAP

Pathogenic

0.83

MetaRNN

Pathogenic

0.88

D;D

MetaSVM

Uncertain

-0.095

MutationAssessor

Pathogenic

3.0

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.023

D;D

Polyphen

1.0

D;.

Vest4

0.58

MVP

0.71

MPC

2.0

ClinPred

0.96

GERP RS

4.7

Varity_R

0.77

gMVP

0.88

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