chr2-222497761-A-C

Position:

• chr2-222497761-A-C

Variant summary

Our verdict is Benign. Variant got -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

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 (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGPP2	NM_152386.4	c.378+23035A>C		intron_variant		ENST00000321276.8	NP_689599.2
SGPP2	NM_001320833.2	c.-7+23035A>C		intron_variant			NP_001307762.1
SGPP2	NM_001320834.2	c.-7+23035A>C		intron_variant			NP_001307763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGPP2	ENST00000321276.8	c.378+23035A>C		intron_variant		1	NM_152386.4	ENSP00000315137	P1

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

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.980

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.978

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.795

Alfa AF: 0.812 Hom.: 11744

Bravo AF: 0.738

Asia WGS AF: 0.918 AC: 3193 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	4.1
DANN	Benign	0.84

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: rs4674659; hg19: chr2-223362480;