rs3745268
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_004230.4(S1PR2):c.179G>A(p.Arg60Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000217 in 1,614,246 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00022 ( 1 hom. )
Consequence
S1PR2
NM_004230.4 missense
NM_004230.4 missense
Scores
1
7
7
Clinical Significance
Conservation
PhyloP100: 5.01
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 Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.02703464).
BP6
?
Variant 19-10224727-C-T is Benign according to our data. Variant chr19-10224727-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2768748.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
S1PR2 | NM_004230.4 | c.179G>A | p.Arg60Gln | missense_variant | 2/2 | ENST00000646641.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
S1PR2 | ENST00000646641.1 | c.179G>A | p.Arg60Gln | missense_variant | 2/2 | NM_004230.4 | P1 | ||
DNMT1 | ENST00000588952.5 | c.-401-5858G>A | intron_variant | 5 | |||||
DNMT1 | ENST00000592342.5 | c.-284+6477G>A | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152256Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000231 AC: 58AN: 251378Hom.: 0 AF XY: 0.000221 AC XY: 30AN XY: 135890
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GnomAD4 exome AF: 0.000222 AC: 325AN: 1461872Hom.: 1 Cov.: 35 AF XY: 0.000212 AC XY: 154AN XY: 727236
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GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152374Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74514
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Benign
T;.
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
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