ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.408A>G (p.Gln136=) (rs1800360)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000241551 SCV000302519 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001095333 SCV000481136 benign Fanconi anemia, complementation group C 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.
Invitae RCV000396417 SCV000560625 benign Fanconi anemia 2020-12-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000569297 SCV000673294 benign Hereditary cancer-predisposing syndrome 2016-08-29 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588429 SCV000695424 benign not provided 2016-04-29 criteria provided, single submitter clinical testing Variant summary: The FANCC c.408A>G variant affects a non-conserved nucleotide, resulting in a synonymous change. Mutation Taster predicts a benign outcome for this variant, and 5/5 Alamut algorithms predict no significant change to splicing. This variant was found in 807/120880 control chromosomes (36 homozygotes) at a frequency of 0.006676, which is about 4 times the maximal expected frequency of a pathogenic FANCC allele (0.0017678), suggesting this variant is benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant was classified as benign.
Leiden Open Variation Database RCV000588429 SCV001365292 uncertain significance not provided 2020-02-28 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357182 SCV001552561 benign Malignant tumor of breast no assertion criteria provided clinical testing The FANCC p.Gln136= variant was identified in dbSNP (ID: rs1800360) as “With other allele” and in control databases in 2016 (87 homozygous) of 276974 chromosomes at a frequency of 0.007 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 1891 (87 homozygous) of 24020 chromosomes (freq: 0.08), Other in 17 of 6456 chromosomes (freq: 0.003), Latino in 94 of 34404 chromosomes (freq: 0.003), European Non-Finnish in 11 of 126548 chromosomes (freq: 0.00009), and South Asian in 3 of 30774 chromosomes (freq: 0.0001), while the variant was not observed in the Ashkenazi Jewish, East Asian, and European Finnish populations. The p.Gln136= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.

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