rs17496827

chr2-222488727-A-Cchr2-222488727-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152386.4(SGPP2):c.378+14001A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,906 control chromosomes in the GnomAD database, including 17,226 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 0.46 (17226 hom., cov: 32)
• Consequence: SGPP2 NM_152386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

Genes affected

SGPP2 (HGNC:19953): (sphingosine-1-phosphate phosphatase 2) The protein encoded by this gene is a transmembrane protein that degrades the bioactive signaling molecule sphingosine 1-phosphate. The encoded protein is induced during inflammatory responses and has been shown to be downregulated by the microRNA-31 tumor suppressor. Alternative splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGPP2	NM_152386.4	c.378+14001A>C		intron_variant		ENST00000321276.8
SGPP2	NM_001320833.2	c.-7+14001A>C		intron_variant
SGPP2	NM_001320834.2	c.-7+14001A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGPP2	ENST00000321276.8	c.378+14001A>C		intron_variant		1	NM_152386.4	P1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69775 AN: 151788 Hom.: 17217 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.460 AC: 69810 AN: 151906 Hom.: 17226 Cov.: 32 AF XY: 0.464 AC XY: 34444 AN XY: 74236

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.499

Alfa AF: 0.501 Hom.: 11193

Bravo AF: 0.465

Asia WGS AF: 0.539 AC: 1875 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	0.24
Dann	Benign	0.54

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: rs17496827; hg19: chr2-223353446;