14-100146860-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.832

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 -11 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_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.832 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEGS2	NM_206918.3	c.873C>T	p.His291=	synonymous_variant	3/3	ENST00000305631.7
DEGS2	XM_006720043.4	c.765C>T	p.His255=	synonymous_variant	4/4

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00203 AC: 309 AN: 152150 Hom.: 2 Cov.: 33

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.: 2 AF XY: 0.00209 AC XY: 284 AN XY: 135754

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.: 6 Cov.: 32 AF XY: 0.00272 AC XY: 1978 AN XY: 727078

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.: 2 Cov.: 33 AF XY: 0.00191 AC XY: 142 AN XY: 74444

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.: 0

Bravo AF: 0.00210

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00209 AC: 18

ExAC AF: 0.00228 AC: 277

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.15
Cadd	Benign	11
Dann	Uncertain	0.99
Eigen	Benign	0.16
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.0075	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;N
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.036
Sift	Benign	0.18	T
Vest4		0.095
MVP		0.79
ClinPred		0.026	T
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

Other links and lift over

dbSNP: rs140696950; hg19: chr14-100613197;