chr2-222424732-C-T

Variant names:

• chr2-222424732-C-T
• rs964286756
• NM_152386.4:c.130C>T

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.130C>T​(p.Arg44Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000587 in 1,431,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000060 (0 hom.)
• Consequence: SGPP2 NM_152386.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.440
• 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=0.23421979).

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.130C>T	p.Arg44Trp	missense	Exon 1 of 5	NP_689599.2
	SGPP2	NM_001320833.2		c.-398C>T		5_prime_UTR	Exon 1 of 6	NP_001307762.1	Q8IWX5-2
	SGPP2	NM_001320834.2		c.-166+654C>T		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.130C>T	p.Arg44Trp	missense	Exon 1 of 5	ENSP00000315137.7	Q8IWX5-1
	SGPP2	ENST00000964572.1		c.130C>T	p.Arg44Trp	missense	Exon 1 of 5	ENSP00000634631.1
	SGPP2	ENST00000852416.1		c.130C>T	p.Arg44Trp	missense	Exon 1 of 4	ENSP00000522475.1

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 7 AN: 151960 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000312 AC: 2 AN: 64148 AF XY: 0.0000536

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000854

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000602 AC: 77 AN: 1279318 Hom.: 0 Cov.: 30 AF XY: 0.0000701 AC XY: 44 AN XY: 627716

African (AFR) AF: 0.00 AC: 0 AN: 25908

American (AMR) AF: 0.00 AC: 0 AN: 22790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22030

East Asian (EAS) AF: 0.00 AC: 0 AN: 27286

South Asian (SAS) AF: 0.00 AC: 0 AN: 67060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3830

European-Non Finnish (NFE) AF: 0.0000663 AC: 68 AN: 1026072

Other (OTH) AF: 0.000171 AC: 9 AN: 52550

GnomAD4 genome AF: 0.0000461 AC: 7 AN: 151960 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74230

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67940

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.44
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.064
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.99	D
Vest4		0.18
MutPred		0.37		Loss of methylation at R44 (P = 0.0281)
MVP		0.21
MPC		0.17
ClinPred		0.15	T
GERP RS		3.0
PromoterAI		0.0091	Neutral
Varity_R		0.065
gMVP		0.43
Mutation Taster		=99/1	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: rs964286756; hg19: chr2-223289451;