Submissions for variant NM_001127464.2(ZNF469):c.7554del (p.Ser2519Alafs)

dbSNP: rs886039575

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000255934	SCV000322451	likely pathogenic	not provided	2023-03-14	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (gnomAD); Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 1407 amino acids are lost and replaced with 36 incorrect amino acids; This variant is associated with the following publications: (PMID: 26582918, 27535533)
Eurofins Ntd Llc (ga)	RCV000255934	SCV000701818	pathogenic	not provided	2016-10-12	criteria provided, single submitter	clinical testing
Invitae	RCV000255934	SCV002995835	pathogenic	not provided	2022-12-17	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the ZNF469 protein in which other variant(s) (p.Arg3414Glyfs*59) have been determined to be pathogenic (PMID: 32671420). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 265490). This variant has not been reported in the literature in individuals affected with ZNF469-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser2519Alafs*37) in the ZNF469 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1407 amino acid(s) of the ZNF469 protein.