Submissions for variant NM_022725.4(FANCF):c.698_699del (p.Gly233fs)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV004719585	SCV005325991	likely pathogenic	not provided	2024-01-03	criteria provided, single submitter	clinical testing	Reported with a second FANCF variant on the opposite allele (in trans) in a patient with short stature, cafe-au-lait spots, mild anemia, and thrombocytopenia (PMID: 27714961); Frameshift variant predicted to result in abnormal protein length as the last 142 amino acids are replaced with 31 different amino acids; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27714961)
Fulgent Genetics, Fulgent Genetics	RCV005051472	SCV005675945	pathogenic	Fanconi anemia complementation group F	2024-01-04	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV005103589	SCV005847521	pathogenic	Fanconi anemia	2024-05-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly233Glufs*32) in the FANCF gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 142 amino acid(s) of the FANCF protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Fanconi anemia (PMID: 27714961). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant disrupts the C-terminus of the FANCF protein, which is important for proper protein interaction of the FA complex. Experimental studies have shown that disruption of the C-terminus affects FANCF protein function (PMID: 12649160, 11063725, 15262960, 17082180). For these reasons, this variant has been classified as Pathogenic.