19-10223872-G-A
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004230.4(S1PR2):c.1034C>T(p.Thr345Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T345K) has been classified as Uncertain significance.
Frequency
Consequence
NM_004230.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
S1PR2 | NM_004230.4 | c.1034C>T | p.Thr345Met | missense_variant | Exon 2 of 2 | ENST00000646641.1 | NP_004221.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
S1PR2 | ENST00000646641.1 | c.1034C>T | p.Thr345Met | missense_variant | Exon 2 of 2 | NM_004230.4 | ENSP00000496438.1 | |||
DNMT1 | ENST00000588952.5 | c.-401-5003C>T | intron_variant | Intron 1 of 8 | 5 | ENSP00000467050.1 | ||||
DNMT1 | ENST00000592342.5 | c.-284+7332C>T | intron_variant | Intron 1 of 6 | 3 | ENSP00000465993.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD2 exomes AF: 0.0000100 AC: 2AN: 199918 AF XY: 0.00000934 show subpopulations
GnomAD4 exome AF: 0.00000143 AC: 2AN: 1398094Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 689132 show subpopulations
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1034C>T (p.T345M) alteration is located in exon 2 (coding exon 1) of the S1PR2 gene. This alteration results from a C to T substitution at nucleotide position 1034, causing the threonine (T) at amino acid position 345 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with S1PR2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 345 of the S1PR2 protein (p.Thr345Met). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at