2-222424738-C-G

Variant names:

• chr2-222424738-C-G
• rs1027019140
• NM_152386.4:c.136C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152386.4(SGPP2):​c.136C>G​(p.Pro46Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P46S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SGPP2 NM_152386.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10353625).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGPP2	NM_152386.4	MANE Select	c.136C>G	p.Pro46Ala	missense	Exon 1 of 5	NP_689599.2
	SGPP2	NM_001320833.2		c.-392C>G		5_prime_UTR	Exon 1 of 6	NP_001307762.1	Q8IWX5-2
	SGPP2	NM_001320834.2		c.-166+660C>G		intron	N/A	NP_001307763.1	Q8IWX5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGPP2	ENST00000321276.8	TSL:1 MANE Select	c.136C>G	p.Pro46Ala	missense	Exon 1 of 5	ENSP00000315137.7	Q8IWX5-1
	SGPP2	ENST00000964572.1		c.136C>G	p.Pro46Ala	missense	Exon 1 of 5	ENSP00000634631.1
	SGPP2	ENST00000852416.1		c.136C>G	p.Pro46Ala	missense	Exon 1 of 4	ENSP00000522475.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.5
DANN	Benign	0.61
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.44	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.059
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.016
Sift	Benign	0.85	T
Sift4G	Benign	0.53	T
Polyphen		0.15	B
Vest4		0.091
MutPred		0.25		Loss of loop (P = 0.0603)
MVP		0.12
MPC		0.11
ClinPred		0.098	T
GERP RS		3.3
PromoterAI		0.040	Neutral
Varity_R		0.064
gMVP		0.27
Mutation Taster		=96/4	polymorphism

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: rs1027019140; hg19: chr2-223289457;