ClinVar Miner

Submissions for variant NM_001018115.3(FANCD2):c.983G>A (p.Arg328Gln)

gnomAD frequency: 0.00124  dbSNP: rs35625434
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001084208 SCV000291164 benign Fanconi anemia 2021-12-17 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000443739 SCV000511359 likely benign not provided 2016-10-03 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Illumina Laboratory Services,Illumina RCV001146799 SCV001307558 benign Fanconi anemia complementation group D2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000120984 SCV002051021 likely benign not specified 2021-12-10 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000120984 SCV002070976 benign not specified 2020-06-10 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV001084208 SCV002529542 benign Fanconi anemia 2021-05-06 criteria provided, single submitter curation
ITMI RCV000120984 SCV000085152 not provided not specified 2013-09-19 no assertion provided reference population
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120984 SCV001550817 benign not specified no assertion criteria provided clinical testing The FANCD2 p.Arg328Gln variant was identified in 1 of 48 proband chromosomes (frequency: 0.021) from individuals with Fanconi anemia (Nie_2019). The p.R328Q variant was identified as a heterozygous variant in a patient with multiple primary malignant neoplasms who also carried multiple variants in other cancer genes, including BRCA2 and MLH3 (Wang_2019_PMID:30942098). The variant was identified in dbSNP (ID: rs35625434) and ClinVar (classified as benign by Invitae and likely benign by Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics) but was not identified in Cosmic. The variant was identified in control databases in 1133 of 268136 chromosomes (11 homozygous) at a frequency of 0.004225 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1, non-cancer). The variant was observed in the following populations: Latino in 711 of 35082 chromosomes (freq: 0.02027), South Asian in 243 of 30516 chromosomes (freq: 0.007963), East Asian in 147 of 19252 chromosomes (freq: 0.007636), Other in 22 of 6696 chromosomes (freq: 0.003286), African in 5 of 23600 chromosomes (freq: 0.000212) and European (non-Finnish) in 5 of 118032 chromosomes (freq: 0.000042), but was not observed in the Ashkenazi Jewish, or European (Finnish) populations. The p.Arg328 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and three of four in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.