chr8-107901150-TTTCTTG-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_178565.5(RSPO2):c.651_656delCAAGAA(p.Asn217_Lys218del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000137 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
RSPO2
NM_178565.5 disruptive_inframe_deletion
NM_178565.5 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.19
Genes affected
RSPO2 (HGNC:28583): (R-spondin 2) This gene encodes a member of the R-spondin family of proteins. These proteins are secreted ligands of leucine-rich repeat containing G protein-coupled receptors that enhance Wnt signaling through the inhibition of ubiquitin E3 ligases. A chromosomal translocation including this locus that results in the formation of a gene fusion has been identified in multiple human cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| RSPO2 | NM_178565.5 | c.651_656delCAAGAA | p.Asn217_Lys218del | disruptive_inframe_deletion | 6/6 | ENST00000276659.10 | NP_848660.3 | |
| RSPO2 | NM_001282863.2 | c.459_464delCAAGAA | p.Asn153_Lys154del | disruptive_inframe_deletion | 5/5 | NP_001269792.1 | ||
| RSPO2 | NM_001317942.2 | c.450_455delCAAGAA | p.Asn150_Lys151del | disruptive_inframe_deletion | 5/5 | NP_001304871.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000804 AC: 2AN: 248772Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134676
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461788Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727186
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Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 22, 2022 | This variant, c.651_656del, results in the deletion of 2 amino acid(s) of the RSPO2 protein (p.Asn217_Lys218del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs750112556, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RSPO2-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at