chr2-222424787-C-T

Variant names:

• chr2-222424787-C-T
• rs938410747
• NM_152386.4:c.185C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001320833.2(SGPP2):​c.-343C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000716 in 1,396,224 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000077 (1 hom.)
• Consequence: SGPP2 NM_001320833.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.236
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10859963).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320833.2. 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.185C>T	p.Pro62Leu	missense	Exon 1 of 5	NP_689599.2
	SGPP2	NM_001320833.2		c.-343C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001307762.1	Q8IWX5-2
	SGPP2	NM_001320833.2		c.-343C>T		5_prime_UTR	Exon 1 of 6	NP_001307762.1	Q8IWX5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGPP2	ENST00000321276.8	TSL:1 MANE Select	c.185C>T	p.Pro62Leu	missense	Exon 1 of 5	ENSP00000315137.7	Q8IWX5-1
	SGPP2	ENST00000964572.1		c.185C>T	p.Pro62Leu	missense	Exon 1 of 5	ENSP00000634631.1
	SGPP2	ENST00000852416.1		c.185C>T	p.Pro62Leu	missense	Exon 1 of 4	ENSP00000522475.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152022 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000470 AC: 2 AN: 42534 AF XY: 0.00

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: 0.0000772 AC: 96 AN: 1244094 Hom.: 1 Cov.: 30 AF XY: 0.0000871 AC XY: 53 AN XY: 608816

African (AFR) AF: 0.00 AC: 0 AN: 25110

American (AMR) AF: 0.0000557 AC: 1 AN: 17938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20208

East Asian (EAS) AF: 0.00 AC: 0 AN: 27074

South Asian (SAS) AF: 0.000283 AC: 17 AN: 60112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30590

Middle Eastern (MID) AF: 0.000829 AC: 3 AN: 3618

European-Non Finnish (NFE) AF: 0.0000704 AC: 71 AN: 1008716

Other (OTH) AF: 0.0000789 AC: 4 AN: 50728

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74386

African (AFR) AF: 0.00 AC: 0 AN: 41550

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67954

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000340

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	0.098
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.59	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.24
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.092
Sift	Benign	0.29	T
Sift4G	Benign	0.30	T
Polyphen		0.0060	B
Vest4		0.18
MutPred		0.30		Gain of helix (P = 0.0034)
MVP		0.39
MPC		0.12
ClinPred		0.045	T
GERP RS		2.6
PromoterAI		0.013	Neutral
Varity_R		0.032
gMVP		0.39
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: rs938410747; hg19: chr2-223289506;