chr2-222424723-C-T

Variant names:

• chr2-222424723-C-T
• rs749337921
• NM_152386.4:c.121C>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.121C>T​(p.Arg41Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,285,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000031 (0 hom.)
• Consequence: SGPP2 NM_152386.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0160
• 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=0.07726076).

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.121C>T	p.Arg41Cys	missense	Exon 1 of 5	NP_689599.2
	SGPP2	NM_001320833.2		c.-407C>T		5_prime_UTR	Exon 1 of 6	NP_001307762.1	Q8IWX5-2
	SGPP2	NM_001320834.2		c.-166+645C>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.121C>T	p.Arg41Cys	missense	Exon 1 of 5	ENSP00000315137.7	Q8IWX5-1
	SGPP2	ENST00000964572.1		c.121C>T	p.Arg41Cys	missense	Exon 1 of 5	ENSP00000634631.1
	SGPP2	ENST00000852416.1		c.121C>T	p.Arg41Cys	missense	Exon 1 of 4	ENSP00000522475.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000151 AC: 1 AN: 66392 AF XY: 0.0000259

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000311 AC: 4 AN: 1285198 Hom.: 0 Cov.: 30 AF XY: 0.00000317 AC XY: 2 AN XY: 631000

African (AFR) AF: 0.0000769 AC: 2 AN: 26010

American (AMR) AF: 0.00 AC: 0 AN: 23586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22374

East Asian (EAS) AF: 0.00 AC: 0 AN: 27330

South Asian (SAS) AF: 0.0000147 AC: 1 AN: 68198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3838

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1029070

Other (OTH) AF: 0.0000189 AC: 1 AN: 52830

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000536 AC: 1

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	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.016
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.032
Sift	Benign	0.075	T
Sift4G	Benign	0.10	T
Polyphen		0.56	P
Vest4		0.11
MutPred		0.31		Loss of solvent accessibility (P = 0.001)
MVP		0.18
MPC		0.16
ClinPred		0.053	T
GERP RS		-2.0
PromoterAI		0.034	Neutral
Varity_R		0.051
gMVP		0.36
Mutation Taster		=100/0	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: rs749337921; hg19: chr2-223289442;