Submissions for variant NM_173076.3(ABCA12):c.2273dup (p.Leu758fs)

dbSNP: rs1064794286

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000485216	SCV000568669	likely pathogenic	not provided	2017-11-02	criteria provided, single submitter	clinical testing	The c.2273dupT likely pathogenic variant in the ABCA12 gene has been reported previously as the sole identifiable variant in a patient with Harlequin ichthyosis (Thomas et al., 2006). It causes a frameshift starting with codon Leucine 758, changes this amino acid to a Phenylalanine residue, and creates a premature Stop codon at position 4 of the new reading frame, denoted p.Leu758PhefsX4. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In addition, the c.2273dupT variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.2273dupT as a likely pathogenic variant
Invitae	RCV000485216	SCV004293949	pathogenic	not provided	2023-08-04	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 420096). This variant is also known as 2274insT. This premature translational stop signal has been observed in individual(s) with harlequin ichthyosis (PMID: 16902423). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu758Phefs*4) in the ABCA12 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCA12 are known to be pathogenic (PMID: 20672373).