Variant 14-100149369-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_206918.3(DEGS2):c.424G>A(p.Val142Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000984 in 1,606,302 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

DEGS2
NM_206918.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.12

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:

Genome browser will be placed here

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 linkuse as main transcript	c.424G>A	p.Val142Met	missense_variant	2/3	ENST00000305631.7
DEGS2	XM_006720043.4 linkuse as main transcript	c.316G>A	p.Val106Met	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DEGS2	ENST00000305631.7 linkuse as main transcript	c.424G>A	p.Val142Met	missense_variant	2/3	1	NM_206918.3	P1
DEGS2	ENST00000553834.1 linkuse as main transcript	c.83-2462G>A		intron_variant		3
DEGS2	ENST00000557117.1 linkuse as main transcript	n.456G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000700

AC:

AN:

243000

Hom.:

AF XY:

0.0000529

AC XY:

AN XY:

132296

show subpopulations

Gnomad AFR exome

AF:

0.000445

Gnomad AMR exome

AF:

0.0000587

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000552

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000873

AC:

127

AN:

1453934

Hom.:

Cov.:

AF XY:

0.0000706

AC XY:

AN XY:

722178

show subpopulations

Gnomad4 AFR exome

AF:

0.000539

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000885

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.000203

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000852

Hom.:

Bravo

AF:

0.000159

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000744

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 24, 2022

The c.424G>A (p.V142M) alteration is located in exon 2 (coding exon 2) of the DEGS2 gene. This alteration results from a G to A substitution at nucleotide position 424, causing the valine (V) at amino acid position 142 to be replaced by a methionine (M). 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

0.37

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.24

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.31

Sift

Benign

0.19

Sift4G

Benign

0.18

Polyphen

1.0

Vest4

0.47

MVP

0.74

MPC

1.4

ClinPred

0.21

GERP RS

4.4

Varity_R

0.20

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