2-222497761-A-C

Variant names:

• chr2-222497761-A-C
• rs4674659
• NM_152386.4:c.378+23035A>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+23035A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,198 control chromosomes in the GnomAD database, including 49,712 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 0.77 (49712 hom., cov: 32)
• Consequence: SGPP2 NM_152386.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.828
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.958 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+23035A>C		intron	N/A	NP_689599.2
	SGPP2	NM_001320833.2		c.-7+23035A>C		intron	N/A	NP_001307762.1
	SGPP2	NM_001320834.2		c.-7+23035A>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+23035A>C		intron	N/A	ENSP00000315137.7

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116466 AN: 152080 Hom.: 49707 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.978

Gnomad MID AF: 0.860

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.793

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

GnomAD4 genome AF: 0.765 AC: 116504 AN: 152198 Hom.: 49712 Cov.: 32 AF XY: 0.772 AC XY: 57465 AN XY: 74398

African (AFR) AF: 0.348 AC: 14454 AN: 41482

American (AMR) AF: 0.858 AC: 13114 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3105 AN: 3468

East Asian (EAS) AF: 0.980 AC: 5077 AN: 5180

South Asian (SAS) AF: 0.945 AC: 4559 AN: 4826

European-Finnish (FIN) AF: 0.978 AC: 10382 AN: 10618

Middle Eastern (MID) AF: 0.860 AC: 251 AN: 292

European-Non Finnish (NFE) AF: 0.926 AC: 62995 AN: 68016

Other (OTH) AF: 0.795 AC: 1680 AN: 2114

Alfa AF: 0.852 Hom.: 19363

Bravo AF: 0.738

Asia WGS AF: 0.918 AC: 3193 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	4.1
DANN	Benign	0.84
PhyloP100		0.83
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: rs4674659; hg19: chr2-223362480;