ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1485G>A (p.Leu495=) (rs56082100)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000124975 SCV000168415 benign not specified 2014-02-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000205120 SCV000261502 benign Fanconi anemia 2020-12-06 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000124975 SCV000345076 likely benign not specified 2016-08-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV000567268 SCV000673305 likely benign Hereditary cancer-predisposing syndrome 2017-08-19 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Illumina Clinical Services Laboratory,Illumina RCV001167959 SCV001330510 likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356823 SCV001552092 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The FANCC p.Leu495= variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP (rs56082100) as “with likely benign, other allele” and ClinVar (classified as benign by Invitae and GeneDx; and as likely benign by Ambry Genetics and Eurofins). The variant was identified in control databases in 161 of 282,768 chromosomes at a frequency of 0.0006 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 153 of 24,950 chromosomes (freq: 0.006), Latino in 7 of 35,438 chromosomes (freq: 0.0002), and Other in 1 of 7220 chromosomes (freq: 0.0001); it was not observed in the Ashkenazi Jewish, East Asian, Finnish, European or South Asian populations. The p.Leu495= 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. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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