rs769989932

Variant names:

• chr14-100149482-C-G
• rs769989932
• NM_206918.3:c.311G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-100149482-C-G
• chr14-100149482-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_206918.3(DEGS2):​c.311G>C​(p.Arg104Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R104H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 35)
• Consequence: DEGS2 NM_206918.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.744
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206918.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEGS2	NM_206918.3	MANE Select	c.311G>C	p.Arg104Pro	missense	Exon 2 of 3	NP_996801.2	Q6QHC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEGS2	ENST00000305631.7	TSL:1 MANE Select	c.311G>C	p.Arg104Pro	missense	Exon 2 of 3	ENSP00000307126.5	Q6QHC5
	DEGS2	ENST00000553834.1	TSL:3	c.83-2575G>C		intron	N/A	ENSP00000450637.1	G3V2F9
	DEGS2	ENST00000557117.1	TSL:2	n.343G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.5
DANN	Benign	0.91
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.89
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N
PhyloP100		0.74
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.13
Sift	Benign	0.19	T
Sift4G	Benign	0.21	T
Polyphen		0.52	P
Vest4		0.41
MutPred		0.58		Loss of MoRF binding (P = 0.0067)
MVP		0.25
MPC		1.6
ClinPred		0.24	T
GERP RS		-1.3
Varity_R		0.21
gMVP		0.89
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs769989932; hg19: chr14-100615819;