chr14-100148786-G-A

Position:

• chr14-100148786-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_206918.3(DEGS2):​c.825+182C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 152,354 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.023 (64 hom., cov: 35)
• Consequence: DEGS2 NM_206918.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.904

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 (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0233 (3549/152354) while in subpopulation NFE AF= 0.0344 (2342/68030). AF 95% confidence interval is 0.0333. There are 64 homozygotes in gnomad4. There are 1703 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEGS2	NM_206918.3	c.825+182C>T		intron_variant		ENST00000305631.7	NP_996801.2
DEGS2	XM_006720043.4	c.717+182C>T		intron_variant			XP_006720106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEGS2	ENST00000305631.7	c.825+182C>T		intron_variant		1	NM_206918.3	ENSP00000307126	P1
DEGS2	ENST00000553834.1	c.83-1879C>T		intron_variant		3		ENSP00000450637

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3550 AN: 152236 Hom.: 64 Cov.: 35

Gnomad AFR AF: 0.00593

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0344

Gnomad OTH AF: 0.0229

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0233 AC: 3549 AN: 152354 Hom.: 64 Cov.: 35 AF XY: 0.0229 AC XY: 1703 AN XY: 74500

Gnomad4 AFR AF: 0.00591

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.0114

Gnomad4 SAS AF: 0.00310

Gnomad4 FIN AF: 0.0277

Gnomad4 NFE AF: 0.0344

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0283 Hom.: 10

Bravo AF: 0.0227

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.60
DANN	Benign	0.70

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: rs878077; hg19: chr14-100615123;