1-54887064-C-CGGCG
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_014762.4(DHCR24):c.55_56insCGCC(p.Arg19ProfsTer69) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,610,908 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R19R) has been classified as Likely benign.
Frequency
Consequence
NM_014762.4 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000415 AC: 1AN: 240794Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 130894
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458714Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 725452
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74342
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 29, 2022 | Variant summary: DHCR24 c.55_56insCGCC (p.Arg19ProfsX69) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. To our knowledge only a few truncations have been reported in affected individuals, with limited phenotype details (PMID 33027564, 34930662) therefore current evidence is not sufficient to clearly establish whether loss-of-function variant can cause disease. The variant allele was found at a frequency of 4.2e-06 in 240794 control chromosomes (gnomAD). However, this frequency does not allow conclusions about variant significance. To our knowledge, no occurrence of c.55_56insCGCC in individuals affected with Desmosterolosis and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at