Submissions for variant NM_000484.4(APP):c.2212-11_2212-10del

gnomAD frequency: 0.00206  dbSNP: rs112965435

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000710593	SCV000840835	benign	not provided	2017-12-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079143	SCV001018821	benign	Alzheimer disease	2024-12-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001579410	SCV004028726	benign	not specified	2024-09-30	criteria provided, single submitter	clinical testing	Variant summary: APP c.2212-11_2212-10delTT alters a nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00079 in 250828 control chromosomes, predominantly at a frequency of 0.0055 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in APP causing Alzheimer Disease phenotype. c.2212-11_2212-10delTT has been reported in the literature in individuals affected with Alzheimer Disease. These report(s) do not provide unequivocal conclusions about association of the variant with Alzheimer Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 585433). Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000710593	SCV004562330	benign	not provided	2023-11-09	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000710593	SCV001800752	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579410	SCV001807131	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000710593	SCV001965625	likely benign	not provided		no assertion criteria provided	clinical testing