rs7157599

Positions:

• chr14-100159565-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206918.3(DEGS2):​c.23G>A​(p.Ser8Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 1,499,636 control chromosomes in the GnomAD database, including 390,165 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.76 (43764 hom., cov: 33)
  • Exomes 𝑓: 0.72 (346401 hom.)
• Consequence: DEGS2 NM_206918.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.1442915E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEGS2	NM_206918.3	c.23G>A	p.Ser8Asn	missense_variant	1/3	ENST00000305631.7	NP_996801.2
DEGS2	XM_006720043.4	c.-27+7040G>A		intron_variant			XP_006720106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEGS2	ENST00000305631.7	c.23G>A	p.Ser8Asn	missense_variant	1/3	1	NM_206918.3	ENSP00000307126.5
DEGS2	ENST00000553834.1	c.23G>A	p.Ser8Asn	missense_variant	1/2	3		ENSP00000450637.1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114786 AN: 151862 Hom.: 43712 Cov.: 33

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.721

GnomAD3 exomes AF: 0.732 AC: 75145 AN: 102614 Hom.: 27676 AF XY: 0.727 AC XY: 41001 AN XY: 56394

Gnomad AFR exome AF: 0.849

Gnomad AMR exome AF: 0.791

Gnomad ASJ exome AF: 0.681

Gnomad EAS exome AF: 0.736

Gnomad SAS exome AF: 0.732

Gnomad FIN exome AF: 0.727

Gnomad NFE exome AF: 0.706

Gnomad OTH exome AF: 0.708

GnomAD4 exome AF: 0.716 AC: 964931 AN: 1347656 Hom.: 346401 Cov.: 47 AF XY: 0.716 AC XY: 476044 AN XY: 664538

Gnomad4 AFR exome AF: 0.849

Gnomad4 AMR exome AF: 0.783

Gnomad4 ASJ exome AF: 0.677

Gnomad4 EAS exome AF: 0.762

Gnomad4 SAS exome AF: 0.735

Gnomad4 FIN exome AF: 0.737

Gnomad4 NFE exome AF: 0.708

Gnomad4 OTH exome AF: 0.717

GnomAD4 genome AF: 0.756 AC: 114895 AN: 151980 Hom.: 43764 Cov.: 33 AF XY: 0.758 AC XY: 56288 AN XY: 74306

Gnomad4 AFR AF: 0.848

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.735

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.710

Gnomad4 OTH AF: 0.722

Alfa AF: 0.715 Hom.: 27524

Bravo AF: 0.761

TwinsUK AF: 0.709 AC: 2629

ALSPAC AF: 0.708 AC: 2727

ESP6500AA AF: 0.862 AC: 2896

ESP6500EA AF: 0.753 AC: 4583

ExAC AF: 0.667 AC: 16701

Asia WGS AF: 0.768 AC: 2670 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.14	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.40	T;T
MetaRNN	Benign	6.1e-7	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.28	N;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.18	N;N
REVEL	Benign	0.058
Sift	Benign	0.48	T;T
Sift4G	Benign	0.57	T;T
Polyphen		0.0	B;.
Vest4		0.086
MPC		0.65
ClinPred		0.0021	T
GERP RS		0.46
Varity_R		0.057
gMVP		0.50

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

Other links and lift over

dbSNP: rs7157599; hg19: chr14-100625902; COSMIC: COSV59783274; COSMIC: COSV59783274;