Genetic Variant DEGS2:p.Arg104His (chr14-100149482-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_206918.3(DEGS2):c.311G>A(p.Arg104His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000047 in 1,595,658 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R104P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

DEGS2
NM_206918.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.744

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18410107).

BP6

Variant 14-100149482-C-T is Benign according to our data. Variant chr14-100149482-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3500850.Status of the report is criteria_provided_single_submitter, 1 stars.

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>A	p.Arg104His	missense	Exon 2 of 3	NP_996801.2	Q6QHC5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DEGS2	ENST00000305631.7	TSL:1 MANE Select	c.311G>A	p.Arg104His	missense	Exon 2 of 3	ENSP00000307126.5	Q6QHC5
DEGS2	ENST00000553834.1	TSL:3	c.83-2575G>A		intron	N/A	ENSP00000450637.1	G3V2F9
DEGS2	ENST00000557117.1	TSL:2	n.343G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000318

AC:

AN:

220298

AF XY:

0.00000830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000713

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000492

AC:

AN:

1443418

Hom.:

Cov.:

AF XY:

0.0000419

AC XY:

AN XY:

716342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33228

American (AMR)

AF:

0.00

AC:

AN:

42672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25470

East Asian (EAS)

AF:

0.00

AC:

AN:

39112

South Asian (SAS)

AF:

0.00

AC:

AN:

84332

European-Finnish (FIN)

AF:

0.0000202

AC:

AN:

49496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.0000625

AC:

AN:

1103770

Other (OTH)

AF:

0.0000168

AC:

AN:

59604

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000569

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000167

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.6

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.14

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.68

M_CAP

Benign

0.0047

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.65

PhyloP100

0.74

PrimateAI

Benign

0.23

PROVEAN

Benign

0.47

REVEL

Benign

0.035

Sift

Benign

0.57

Sift4G

Benign

0.58

Polyphen

0.0

Vest4

0.10

MutPred

0.52

Loss of methylation at R104 (P = 0.0312)

MVP

0.095

MPC

0.86

ClinPred

0.028

GERP RS

-1.3

Varity_R

0.021

gMVP

0.44

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over