2-218782184-T-TG
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000784.4(CYP27A1):c.4dupG(p.Ala2GlyfsTer179) variant causes a frameshift 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 Pathogenic (★).
Frequency
Consequence
NM_000784.4 frameshift
Scores
Clinical Significance
Conservation
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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 |
---|---|---|---|---|---|---|---|---|---|---|
CYP27A1 | ENST00000258415.9 | c.4dupG | p.Ala2GlyfsTer179 | frameshift_variant | Exon 1 of 9 | 1 | NM_000784.4 | ENSP00000258415.4 | ||
CYP27A1 | ENST00000445971.1 | n.4dupG | non_coding_transcript_exon_variant | Exon 1 of 5 | 5 | ENSP00000404945.1 | ||||
CYP27A1 | ENST00000466602.1 | n.13dupG | non_coding_transcript_exon_variant | Exon 1 of 3 | 2 | |||||
CYP27A1 | ENST00000494263.5 | n.438dupG | non_coding_transcript_exon_variant | Exon 1 of 7 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Cholestanol storage disease Pathogenic:1
This sequence change creates a premature translational stop signal (p.Ala2Glyfs*179) in the CYP27A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYP27A1 are known to be pathogenic (PMID: 9392430, 10775536, 26937392). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CYP27A1-related conditions. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.