rs1553769144
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The ENST00000639785.2(CASR):c.2597_2598delinsTT(p.Arg866Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R866C) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000639785.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CASR | NM_000388.4 | c.2597_2598delinsTT | p.Arg866Leu | missense_variant | 7/7 | ENST00000639785.2 | NP_000379.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.2597_2598delinsTT | p.Arg866Leu | missense_variant | 7/7 | 1 | NM_000388.4 | ENSP00000491584 | P1 | |
CASR | ENST00000498619.4 | c.2627_2628delinsTT | p.Arg876Leu | missense_variant | 7/7 | 1 | ENSP00000420194 | |||
CASR | ENST00000490131.7 | c.2366_2367delinsTT | p.Arg789Leu | missense_variant | 5/5 | 5 | ENSP00000418685 | |||
CASR | ENST00000638421.1 | c.2597_2598delinsTT | p.Arg866Leu | missense_variant | 7/7 | 5 | ENSP00000492190 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Autosomal dominant hypocalcemia 1;C1809471:Familial hypocalciuric hypercalcemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 17, 2017 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CASR-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with leucine at codon 866 of the CASR protein (p.Arg866Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at