19-48626060-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_020126.5(SPHK2):c.209C>T(p.Thr70Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,613,248 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 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 1 hom. )
Consequence
SPHK2
NM_020126.5 missense
NM_020126.5 missense
Scores
2
7
9
Clinical Significance
Conservation
PhyloP100: 3.35
Genes affected
SPHK2 (HGNC:18859): (sphingosine kinase 2) This gene encodes one of two sphingosine kinase isozymes that catalyze the phosphorylation of sphingosine into sphingosine 1-phosphate. Sphingosine 1-phosphate mediates many cellular processes including migration, proliferation and apoptosis, and also plays a role in several types of cancer by promoting angiogenesis and tumorigenesis. The encoded protein may play a role in breast cancer proliferation and chemoresistance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3533076).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPHK2 | NM_020126.5 | c.209C>T | p.Thr70Ile | missense_variant | 3/7 | ENST00000245222.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPHK2 | ENST00000245222.9 | c.209C>T | p.Thr70Ile | missense_variant | 3/7 | 1 | NM_020126.5 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000125 AC: 31AN: 248928Hom.: 0 AF XY: 0.0000888 AC XY: 12AN XY: 135072
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GnomAD4 exome AF: 0.000143 AC: 209AN: 1461032Hom.: 1 Cov.: 31 AF XY: 0.000144 AC XY: 105AN XY: 726820
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74372
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 28, 2021 | The c.209C>T (p.T70I) alteration is located in exon 3 (coding exon 2) of the SPHK2 gene. This alteration results from a C to T substitution at nucleotide position 209, causing the threonine (T) at amino acid position 70 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;T;D;D;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;.;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;.;.;.;.
REVEL
Benign
Sift
Pathogenic
D;.;.;.;.;.;.
Sift4G
Uncertain
D;D;D;D;D;D;D
Polyphen
D;.;D;.;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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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