Submissions for variant NM_004629.2(FANCG):c.1652_1655del (p.Tyr551fs)

dbSNP: rs770263417

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002037622	SCV002231779	pathogenic	Fanconi anemia	2023-10-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr551Phefs*7) in the FANCG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCG are known to be pathogenic (PMID: 12552564). This variant is present in population databases (rs770263417, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with FANCG-related conditions. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003464290	SCV004199135	likely pathogenic	Fanconi anemia complementation group G	2023-08-08	criteria provided, single submitter	clinical testing
Human Genetics Section, Sidra Medicine	RCV003464290	SCV005077818	pathogenic	Fanconi anemia complementation group G		criteria provided, single submitter	research	Clarification (August 6, 2024): Franklin and VarSome were utilized as supplementary tools to predict the pathogenicity of the identified variant. The patient exhibited the following symptoms: Skin: Café-au-lait spots, Growth retardation, and short stature. Consequently, Whole Genome Sequencing (WGS) was performed, which identified the variant responsible for the observed phenotypes. We are currently preparing the publication detailing these findings, and the PubMed ID (PMID) will be provided upon its release.
GeneDx	RCV004719208	SCV005325955	pathogenic	not provided	2023-07-05	criteria provided, single submitter	clinical testing	Reported in the germline of a patient with pancreatic cancer, however a second FANCG variant was not identified (Smith et al., 2016); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 26546047)
Neuberg Centre For Genomic Medicine, NCGM	RCV003464290	SCV005329592	likely pathogenic	Fanconi anemia complementation group G	2023-05-20	criteria provided, single submitter	clinical testing	The frameshift variant c.1652_1655del(p.Tyr551PhefsTer7) in FANCG gene has been submitted to ClinVar database as Pathogenic. The observed variant has allele frequency of 0.0008% in gnomAD exomes database. This variant causes a frameshift starting with codon Tyrosine 551, changes this amino acid to Phenylalanine residue, and creates a premature Stop codon at position 7 of the new reading frame, denoted p.Tyr551PhefsTer7. This variant is predicted to cause loss of normal protein function through protein truncation. Loss-of-function variants in FANCG are known to be pathogenic (Auerbach AD et. al., 2003). However, functional studies will be required to confirm the pathogenicity of the variant. For these reasons, this variant has been classified as Likely Pathogenic.