2-222488727-A-C

Variant names:

• chr2-222488727-A-C
• rs17496827
• NM_152386.4:c.378+14001A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152386.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGPP2	NM_152386.4	MANE Select	c.378+14001A>C		intron	N/A	NP_689599.2
	SGPP2	NM_001320833.2		c.-7+14001A>C		intron	N/A	NP_001307762.1
	SGPP2	NM_001320834.2		c.-7+14001A>C		intron	N/A	NP_001307763.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGPP2	ENST00000321276.8	TSL:1 MANE Select	c.378+14001A>C		intron	N/A	ENSP00000315137.7

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

African (AFR) AF: 0.276 AC: 11432 AN: 41428

American (AMR) AF: 0.612 AC: 9345 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1974 AN: 3472

East Asian (EAS) AF: 0.494 AC: 2541 AN: 5148

South Asian (SAS) AF: 0.576 AC: 2769 AN: 4808

European-Finnish (FIN) AF: 0.500 AC: 5272 AN: 10534

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34711 AN: 67938

Other (OTH) AF: 0.499 AC: 1054 AN: 2114

Alfa AF: 0.480 Hom.: 18865

Bravo AF: 0.465

Asia WGS AF: 0.539 AC: 1875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.24
DANN	Benign	0.54
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs17496827; hg19: chr2-223353446;