Submissions for variant NM_004629.2(FANCG):c.1538G>A (p.Arg513Gln)

gnomAD frequency: 0.00863  dbSNP: rs17885240

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000229666	SCV000288623	benign	Fanconi anemia	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000317116	SCV000484369	likely benign	Inclusion Body Myopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000353275	SCV000484370	likely benign	Amyotrophic Lateral Sclerosis, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000121035	SCV000594705	benign	not specified	2016-11-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001168311	SCV001330891	uncertain significance	Fanconi anemia complementation group G	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab	RCV001168311	SCV001653325	likely benign	Fanconi anemia complementation group G	2021-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001194965	SCV001834775	likely benign	not provided	2020-10-08	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26033879, 12552564, 16643430)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000121035	SCV003844910	benign	not specified	2023-02-17	criteria provided, single submitter	clinical testing	Variant summary: FANCG c.1538G>A (p.Arg513Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0083 in 251472 control chromosomes in the gnomAD database, including 14 homozygotes. The observed variant frequency is approximately 9.41 fold of the estimated maximal expected allele frequency for a pathogenic variant in FANCG causing Fanconi Anemia phenotype (0.00088), strongly suggesting that the variant is benign. c.1538G>A has been reported in the literature in individuals affected with Fanconi Anemia and Acute Myeloid Leukemia (e.g., Meyer_2006, Nicchia_2015) however without strong evidence for causality. These reports therefore do not provide conclusions about association of the variant with Fanconi Anemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight ClinVar submitters (evaluation after 2014) have reported the variant with conflicting assessments: three cite the variant as benign, three cite the variant as likely benign, one cites the variant as uncertain signficance, and one cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as benign.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001168311	SCV004017686	benign	Fanconi anemia complementation group G	2023-07-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001194965	SCV004157696	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	FANCG: BP4, BS1, BS2
Molecular Genetics, Royal Melbourne Hospital	RCV001168311	SCV004812750	benign	Fanconi anemia complementation group G	2024-01-05	criteria provided, single submitter	clinical testing
ITMI	RCV000121035	SCV000085203	not provided	not specified	2013-09-19	no assertion provided	reference population
PreventionGenetics, part of Exact Sciences	RCV003891643	SCV000310551	benign	FANCG-related disorder	2019-10-09	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Leiden Open Variation Database	RCV001194965	SCV001364839	pathogenic	not provided	2020-02-28	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Johan de Winter.
Natera, Inc.	RCV001168311	SCV001452297	benign	Fanconi anemia complementation group G	2020-09-16	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000121035	SCV001809787	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000121035	SCV001931526	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001194965	SCV002036805	likely benign	not provided		no assertion criteria provided	clinical testing