Submissions for variant NM_001018115.3(FANCD2):c.1367T>G (p.Leu456Arg)

gnomAD frequency: 0.02918  dbSNP: rs35782247

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000120985	SCV000305857	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094941	SCV000439476	likely benign	Fanconi anemia complementation group D2	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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000434788	SCV000511003	benign	not provided	2016-12-14	criteria provided, single submitter	clinical testing
Invitae	RCV000406228	SCV000558538	benign	Fanconi anemia	2023-12-07	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000120985	SCV000603570	benign	not specified	2017-03-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000434788	SCV001849301	benign	not provided	2019-04-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21356188, 27153395, 24728327, 20981092, 17436244)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000120985	SCV002051296	benign	not specified	2021-12-20	criteria provided, single submitter	clinical testing	Variant summary: FANCD2 c.1367T>G (p.Leu456Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.007 in 251396 control chromosomes, predominantly at a frequency of 0.099 within the African or African-American subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 204.49 fold of the estimated maximal expected allele frequency for a pathogenic variant in FANCD2 causing Fanconi Anemia phenotype (0.00048), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, with conflicting interpretation. Based on the evidence outlined above, the variant was classified as benign.
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225375	SCV002505198	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000406228	SCV002529457	benign	Fanconi anemia	2020-09-10	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001094941	SCV004017642	benign	Fanconi anemia complementation group D2	2023-07-07	criteria provided, single submitter	clinical testing
ITMI	RCV000120985	SCV000085153	not provided	not specified	2013-09-19	no assertion provided	reference population
Leiden Open Variation Database	RCV001094941	SCV001364780	pathogenic	Fanconi anemia complementation group D2	2020-02-28	flagged submission	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000434788	SCV001800169	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000120985	SCV001807258	benign	not specified		no assertion criteria provided	clinical testing