rs1553769059
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000388.4(CASR):c.2244delGinsCC(p.Ser749LeufsTer11) variant causes a frameshift, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. P748P) has been classified as Benign.
Frequency
Consequence
NM_000388.4 frameshift, synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.2244delGinsCC | p.Ser749LeufsTer11 | frameshift_variant, synonymous_variant | Exon 7 of 7 | 1 | NM_000388.4 | ENSP00000491584.2 | ||
CASR | ENST00000498619.4 | c.2274delGinsCC | p.Ser759LeufsTer11 | frameshift_variant, synonymous_variant | Exon 7 of 7 | 1 | ENSP00000420194.1 | |||
CASR | ENST00000638421.1 | c.2244delGinsCC | p.Ser749LeufsTer11 | frameshift_variant, synonymous_variant | Exon 7 of 7 | 5 | ENSP00000492190.1 | |||
CASR | ENST00000490131.7 | c.2013delGinsCC | p.Ser672LeufsTer11 | frameshift_variant, synonymous_variant | Exon 5 of 5 | 5 | ENSP00000418685.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 69
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
CASR-related disorder Pathogenic:1
The CASR c.2274delinsCC variant is predicted to result in a frameshift and premature protein termination (p.Ser759Leufs*11). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in CASR are expected to be pathogenic. This variant is interpreted as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at