Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000778450 | SCV000914698 | likely pathogenic | Fanconi anemia complementation group I | 2017-09-06 | criteria provided, single submitter | clinical testing | The FANCI c.3041G>A (p.Cys1014Tyr) missense variant has been reported in three studies in which it is found in a total of six individuals including in three with Fanconi anemia, one in a homozygous state and two in a compound heterozygous state with a second null allele. One of the compound heterozygous individuals was also diagnosed with the VACTERL phenotype. The p.Cys1014Tyr variant was also reported in a heterozygous state in three individuals, one with breast cancer and two with prostate cancer (Ameziane et al. 2012; Mantere et al. 2015; Savage et al. 2016). The p.Cys1014Tyr variant was reported in four of 1365 controls in a heterozygous state and is reported at a frequency of 0.000853 in the European (Finnish) population of the Genome Aggregation Database. Based on the evidence, the p.Cys1014Tyr variant is classified as likely pathogenic for Fanconi anemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Labcorp Genetics |
RCV001239482 | SCV001412358 | pathogenic | Fanconi anemia | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 1014 of the FANCI protein (p.Cys1014Tyr). This variant is present in population databases (rs140404896, gnomAD 0.09%). This missense change has been observed in individual(s) with bone marrow failure and/or Fanconi anemia (PMID: 22720145, 24989076, 26590883, 32054657). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 631744). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000778450 | SCV005057704 | pathogenic | Fanconi anemia complementation group I | 2024-03-14 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000778450 | SCV005631053 | likely pathogenic | Fanconi anemia complementation group I | 2024-04-17 | criteria provided, single submitter | clinical testing |