Our verdict is Pathogenic. Variant got 17 ACMG points: 17P and 0B. PVS1PM2_SupportingPP5_Very_Strong
The NM_000033(ABCD1):c.253dup(p.Arg85ProfsTer110) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. F83F) has been classified as Likely benign.
Verdict is Pathogenic. Variant got 17 ACMG points.
GnomAD3 genomesCov.: 25
Submissions by phenotype
|Pathogenic, criteria provided, single submitter||clinical testing||Invitae||May 05, 2022||This sequence change creates a premature translational stop signal (p.Arg85Profs*110) in the ABCD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCD1 are known to be pathogenic (PMID: 11748843). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of X-linked adrenoleukodystrophy (PMID: 15811009, 27489563). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 162148). For these reasons, this variant has been classified as Pathogenic. -|
|Pathogenic, no assertion criteria provided||research||Faculty of Medicine, Iran University of Medical Sciences (IUMS)||Sep 17, 2014||Present study is the first to report clinical and genetics characteristics of Iranian X-ALD patients, Lorestan province. It also highlighted the importance of genetic counseling through reliable identification of heterozygous as well as homozygote females in consanguineous communities with subsequent elevated prevalence. Unexpectedly, there exist childhood cerebral ALD, adrenomyeloneuropathy, and addison-only disease phenotypes of ALD in our pedigree with the same variant. X-ALD also occurred significantly more in our studied Iranian pedigree compared to its reported prevalence (Odd Ratio 4249.7500, 95% CI 224.6575 to 80390.7075, p-value< 0.0001). -|
|Pathogenic, criteria provided, single submitter||clinical testing||Eurofins Ntd Llc (ga)||Dec 02, 2015||- -|
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