2-222424622-G-A

Position:

• chr2-222424622-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152386.4(SGPP2):​c.20G>A​(p.Ser7Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000802 in 1,247,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: SGPP2 NM_152386.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3328508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGPP2	NM_152386.4	c.20G>A	p.Ser7Asn	missense_variant	1/5	ENST00000321276.8	NP_689599.2
SGPP2	NM_001320833.2	c.-508G>A		5_prime_UTR_variant	1/6		NP_001307762.1
SGPP2	NM_001320834.2	c.-166+544G>A		intron_variant			NP_001307763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGPP2	ENST00000321276.8	c.20G>A	p.Ser7Asn	missense_variant	1/5	1	NM_152386.4	ENSP00000315137.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.02e-7 AC: 1 AN: 1247020 Hom.: 0 Cov.: 30 AF XY: 0.00000164 AC XY: 1 AN XY: 610578

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.96e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

The c.20G>A (p.S7N) 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 20, causing the serine (S) at amino acid position 7 to be replaced by an asparagine (N). 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	0.16
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.084
Sift	Benign	0.39	T
Sift4G	Benign	0.38	T
Polyphen		1.0	D
Vest4		0.15
MutPred		0.21		Loss of phosphorylation at S7 (P = 0.0333);
MVP		0.37
MPC		0.43
ClinPred		0.89	D
GERP RS		4.0
Varity_R		0.14
gMVP		0.42

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: rs1485412980; hg19: chr2-223289341;