Submissions for variant NM_000350.3(ABCA4):c.5161_5162del (p.Thr1721fs)

dbSNP: rs61750566

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000085702	SCV000344533	pathogenic	not provided	2016-09-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000085702	SCV000582480	pathogenic	not provided	2015-09-04	criteria provided, single submitter	clinical testing	The c.5161_5162delAC deletion in the ABCA4 gene has been reported previously in association with Stargardt disease (Maugeri et al., 1999; Papaioannou et al., 2000; Briggs et al., 2001). The deletion causes a frameshift starting with codon Threonine 1721, changes this amino acid to a Histidine residue and creates a premature Stop codon at position 65 of the new reading frame, denoted p.Thr1721HisfsX65. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, we interpret this variant as pathogenic.
Blueprint Genetics	RCV001073781	SCV001239342	pathogenic	Retinal dystrophy	2018-01-12	criteria provided, single submitter	clinical testing
Invitae	RCV000085702	SCV002211098	pathogenic	not provided	2022-04-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Thr1721Hisfs*65) in the ABCA4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCA4 are known to be pathogenic (PMID: 10958761, 24938718, 25312043, 26780318). This variant is present in population databases (rs61750566, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with Stargardt Disease (PMID: 10090887, 25312043, 25444351, 28041643, 29925512). This variant is also known as 5161delAC. ClinVar contains an entry for this variant (Variation ID: 99349). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Retina International	RCV000085702	SCV000117841	not provided	not provided		flagged submission	not provided
Retina International	RCV000085702	SCV000117842	not provided	not provided		no assertion provided	not provided
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000301420	SCV000598991	pathogenic	Severe early-childhood-onset retinal dystrophy	2015-01-01	no assertion criteria provided	research