rs117064827
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_004230.4(S1PR2):āc.857T>Cā(p.Val286Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00871 in 1,570,584 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0065 ( 3 hom., cov: 33)
Exomes š: 0.0089 ( 78 hom. )
Consequence
S1PR2
NM_004230.4 missense
NM_004230.4 missense
Scores
2
5
7
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
S1PR2 (HGNC:3169): (sphingosine-1-phosphate receptor 2) This gene encodes a member of the G protein-coupled receptors, as well as the EDG family of proteins. The encoded protein is a receptor for sphingosine 1-phosphate, which participates in cell proliferation, survival, and transcriptional activation. Defects in this gene have been associated with congenital profound deafness. [provided by RefSeq, Mar 2016]
DNMT1 (HGNC:2976): (DNA methyltransferase 1) This gene encodes an enzyme that transfers methyl groups to cytosine nucleotides of genomic DNA. This protein is the major enzyme responsible for maintaining methylation patterns following DNA replication and shows a preference for hemi-methylated DNA. Methylation of DNA is an important component of mammalian epigenetic gene regulation. Aberrant methylation patterns are found in human tumors and associated with developmental abnormalities. Variation in this gene has been associated with cerebellar ataxia, deafness, and narcolepsy, and neuropathy, hereditary sensory, type IE. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.013470501).
BP6
?
Variant 19-10224049-A-G is Benign according to our data. Variant chr19-10224049-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 506086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-10224049-A-G is described in Lovd as [Likely_benign].
BS2
?
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
S1PR2 | NM_004230.4 | c.857T>C | p.Val286Ala | missense_variant | 2/2 | ENST00000646641.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
S1PR2 | ENST00000646641.1 | c.857T>C | p.Val286Ala | missense_variant | 2/2 | NM_004230.4 | P1 | ||
DNMT1 | ENST00000588952.5 | c.-401-5180T>C | intron_variant | 5 | |||||
DNMT1 | ENST00000592342.5 | c.-284+7155T>C | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00646 AC: 918AN: 142118Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.00728 AC: 1784AN: 245062Hom.: 9 AF XY: 0.00746 AC XY: 993AN XY: 133140
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GnomAD4 exome AF: 0.00893 AC: 12758AN: 1428344Hom.: 78 Cov.: 35 AF XY: 0.00870 AC XY: 6180AN XY: 710202
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GnomAD4 genome ? AF: 0.00645 AC: 918AN: 142240Hom.: 3 Cov.: 33 AF XY: 0.00598 AC XY: 417AN XY: 69788
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 19, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | S1PR2: BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 04, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 23, 2017 | p.Val286Ala in exon 2 of S1PR2: This variant is not expected to have clinical si gnificance because it has been identified in 1.03% (663/64316) of European chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs117064827). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;.
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at