Variant 14-100146860-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_206918.3(DEGS2):c.873C>T(p.His291=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00276 in 1,613,812 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 6 hom. )

Consequence

DEGS2
NM_206918.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.832

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 Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0075268447).

BP6

Variant 14-100146860-G-A is Benign according to our data. Variant chr14-100146860-G-A is described in ClinVar as [Benign]. Clinvar id is 779357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.832 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEGS2	NM_206918.3 linkuse as main transcript	c.873C>T	p.His291=	synonymous_variant	3/3	ENST00000305631.7	NP_996801.2
DEGS2	XM_006720043.4 linkuse as main transcript	c.765C>T	p.His255=	synonymous_variant	4/4		XP_006720106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEGS2	ENST00000305631.7 linkuse as main transcript	c.873C>T	p.His291=	synonymous_variant	3/3	1	NM_206918.3	ENSP00000307126	P1
DEGS2	ENST00000553834.1 linkuse as main transcript	c.130C>T	p.Leu44Phe	missense_variant	2/2	3		ENSP00000450637

Frequencies

GnomAD3 genomes

AF:

0.00203

AC:

309

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00284

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00215

AC:

540

AN:

251140

Hom.:

AF XY:

0.00209

AC XY:

284

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000882

Gnomad FIN exome

AF:

0.00255

Gnomad NFE exome

AF:

0.00310

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00283

AC:

4142

AN:

1461544

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

1978

AN XY:

727078

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.00199

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000742

Gnomad4 FIN exome

AF:

0.00308

Gnomad4 NFE exome

AF:

0.00323

Gnomad4 OTH exome

AF:

0.00287

GnomAD4 genome

AF:

0.00203

AC:

309

AN:

152268

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.00284

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00225

Hom.:

Bravo

AF:

0.00210

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00228

AC:

277

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.16

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.44

M_CAP

Benign

0.016

MetaRNN

Benign

0.0075

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;N

PROVEAN

Benign

-0.47

REVEL

Benign

0.036

Sift

Benign

0.18

Vest4

0.095

MVP

0.79

ClinPred

0.026

GERP RS

3.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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