Submissions for variant NM_001113378.2(FANCI):c.3493del (p.Asp1165fs)

dbSNP: rs758597713

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000457201	SCV000547775	pathogenic	Fanconi anemia	2023-12-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asp1165Thrfs*34) in the FANCI gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCI are known to be pathogenic (PMID: 17452773, 17460694). This variant is present in population databases (rs758597713, gnomAD 0.04%). This premature translational stop signal has been observed in individual(s) with head and neck squamous cell carcinoma (PMID: 28678401). ClinVar contains an entry for this variant (Variation ID: 408200). For these reasons, this variant has been classified as Pathogenic.
AiLife Diagnostics, AiLife Diagnostics	RCV002223210	SCV002501463	pathogenic	not provided	2021-06-11	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000457201	SCV002529840	likely pathogenic	Fanconi anemia	2021-01-23	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV001194983	SCV002811465	pathogenic	Fanconi anemia complementation group I	2021-07-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000457201	SCV002819343	likely pathogenic	Fanconi anemia	2022-12-08	criteria provided, single submitter	clinical testing	Variant summary: FANCI c.3493delG (p.Asp1165ThrfsX34) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been associated with Fanconi Anemia in HGMD. The variant allele was found at a frequency of 5.2e-05 in 251486 control chromosomes. c.3493delG has been reported in the literature as a compound heterozygous genotype in individuals affected with Fanconi Anemia (Chandrasekharappa_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=2) and likely pathogenic (n=1) . Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics	RCV001194983	SCV004197156	pathogenic	Fanconi anemia complementation group I	2023-10-15	criteria provided, single submitter	clinical testing
Leiden Open Variation Database	RCV001194983	SCV001364857	pathogenic	Fanconi anemia complementation group I	2013-10-04	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.