2-222424802-G-A

Variant names:

• chr2-222424802-G-A
• rs1402122405
• NM_152386.4:c.200G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152386.4(SGPP2):​c.200G>A​(p.Arg67His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000408 in 1,226,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SGPP2 NM_152386.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.779

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23460957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGPP2	NM_152386.4	c.200G>A	p.Arg67His	missense_variant	Exon 1 of 5	ENST00000321276.8	NP_689599.2
SGPP2	NM_001320833.2	c.-328G>A		5_prime_UTR_variant	Exon 1 of 6		NP_001307762.1
SGPP2	NM_001320834.2	c.-166+724G>A		intron_variant	Intron 1 of 4		NP_001307763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGPP2	ENST00000321276.8	c.200G>A	p.Arg67His	missense_variant	Exon 1 of 5	1	NM_152386.4	ENSP00000315137.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000408 AC: 5 AN: 1226292 Hom.: 0 Cov.: 30 AF XY: 0.00000501 AC XY: 3 AN XY: 598958

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000178

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000399

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.200G>A (p.R67H) alteration is located in exon 1 (coding exon 1) of the SGPP2 gene. This alteration results from a G to A substitution at nucleotide position 200, causing the arginine (R) at amino acid position 67 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.074
Sift	Uncertain	0.020	D
Sift4G	Benign	0.079	T
Polyphen		0.63	P
Vest4		0.17
MutPred		0.66		Loss of glycosylation at P72 (P = 0.1138);
MVP		0.10
MPC		0.16
ClinPred		0.12	T
GERP RS		0.086
Varity_R		0.11
gMVP		0.35

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: rs1402122405; hg19: chr2-223289521;