Submissions for variant NM_000033.4(ABCD1):c.1415_1416del (p.Gln472fs) (rs387906494)

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Total submissions: 7

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000516943	SCV000109780	pathogenic	not provided	2015-06-10	criteria provided, single submitter	clinical testing
Counsyl	RCV000012055	SCV000486281	pathogenic	Adrenoleukodystrophy	2016-07-12	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000516943	SCV000612228	pathogenic	not provided	2012-08-13	criteria provided, single submitter	clinical testing
GeneDx	RCV000516943	SCV000617388	pathogenic	not provided	2017-05-30	criteria provided, single submitter	clinical testing	The c.1415_1416delAG pathogenic variant in the ABCD1 gene has been previously reported in multiple unrelated individuals as a common variant associated with varying forms of X-linked adrenoleukodystrophy (Kemp et al., 2004; Feigenbaum et al., 1996; Kemp et al., 2001). This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.1415_1416delAG variant causes a frameshift starting with codon Glutamine 472, changes this amino acid to a Arginine residue, and creates a premature Stop codon at position 83 of the new reading frame, denoted p.Gln472ArgfsX83. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, we interpret c.1415_1416delAG as a pathogenic variant.
Invitae	RCV000012055	SCV000629988	pathogenic	Adrenoleukodystrophy	2018-08-27	criteria provided, single submitter	clinical testing	This sequence change deletes 2 nucleotides from exon 5 of the ABCD1 mRNA (c.1415_1416delAG), causing a frameshift at codon 472. This creates a premature translational stop signal (p.Gln472Argfs*83) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCD1 are known to be pathogenic. This particular variant has been reported in the literature in several individuals affected with childhood or adult-onset adrenoleukodystrophy or adrenomyeloneuropathy (PMID: 8048932, 23154058, 23768953, 23566833, 22479560, 7849723). This variant is also referred to as 1801delAG in the literature. ClinVar contains an entry for this variant (Variation ID: 11303). For these reasons, this variant has been classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000516943	SCV000883323	pathogenic	not provided	2017-11-09	criteria provided, single submitter	clinical testing
OMIM	RCV000012055	SCV000032289	pathogenic	Adrenoleukodystrophy	1994-10-01	no assertion criteria provided	literature only

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