chr14-100149261-G-A

Variant names:

• chr14-100149261-G-A
• NM_206918.3:c.532C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_206918.3(DEGS2):​c.532C>T​(p.His178Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 35)
• Consequence: DEGS2 NM_206918.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.333
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13687795).

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.532C>T	p.His178Tyr	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.532C>T	p.His178Tyr	missense	Exon 2 of 3	ENSP00000307126.5	Q6QHC5
	DEGS2	ENST00000553834.1	TSL:3	c.83-2354C>T		intron	N/A	ENSP00000450637.1	G3V2F9
	DEGS2	ENST00000557117.1	TSL:2	n.564C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 35

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	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.049
DANN	Benign	0.48
DEOGEN2	Benign	0.22	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		0.33
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.079
Sift	Benign	0.64	T
Sift4G	Benign	1.0	T
Polyphen		0.57	P
Vest4		0.25
MutPred		0.44		Loss of methylation at K180 (P = 0.0732)
MVP		0.17
MPC		1.3
ClinPred		0.18	T
GERP RS		-3.5
Varity_R		0.060
gMVP		0.77
Mutation Taster		=86/14	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

hg19: chr14-100615598;