chr2-222424787-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.236
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10859963).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SGPP2NM_152386.4 linkc.185C>T p.Pro62Leu missense_variant Exon 1 of 5 ENST00000321276.8 NP_689599.2 Q8IWX5-1
SGPP2NM_001320833.2 linkc.-343C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 6 NP_001307762.1 Q8IWX5-2
SGPP2NM_001320833.2 linkc.-343C>T 5_prime_UTR_variant Exon 1 of 6 NP_001307762.1 Q8IWX5-2
SGPP2NM_001320834.2 linkc.-166+709C>T intron_variant Intron 1 of 4 NP_001307763.1 Q8IWX5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SGPP2ENST00000321276.8 linkc.185C>T p.Pro62Leu missense_variant Exon 1 of 5 1 NM_152386.4 ENSP00000315137.7 Q8IWX5-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152022
Hom.:
0
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.0000470
AC:
2
AN:
42534
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
25296
show subpopulations
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 SAS exome
AF:
0.000213
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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000557
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000283
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000704
Gnomad4 OTH exome
AF:
0.0000789
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152130
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000340

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 19, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.185C>T (p.P62L) alteration is located in exon 1 (coding exon 1) of the SGPP2 gene. This alteration results from a C to T substitution at nucleotide position 185, causing the proline (P) at amino acid position 62 to be replaced by a leucine (L). 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
0.098
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
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
Varity_R
0.032
gMVP
0.39

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs938410747; hg19: chr2-223289506; API