ClinVar Miner

Submissions for variant NM_144966.5(FREM1):c.1640C>G (p.Ala547Gly) (rs201056172)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000377307 SCV000479109 uncertain significance Oculotrichoanal syndrome 2018-01-12 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Cavalleri Lab, Royal College of Surgeons in Ireland RCV001171324 SCV001328271 uncertain significance Chronic kidney disease 2020-05-28 criteria provided, single submitter research PP3, BS1
Sydney Genome Diagnostics,Children's Hospital Westmead RCV001328303 SCV001449325 uncertain significance Congenital anomalies of kidney and urinary tract 2018-02-09 no assertion criteria provided clinical testing This individual is heterozygous for the variant, c.1640C>G p.(Ala547Gly), in the FREM1 gene. To our knowledge, this variant has not been previously reported in the literature or any disease specific databases to be a disease causing variant. This variant has been reported in the gnomAD browser (http://gnomad.broadinstitute.org with a low allele frequency of 0.011% (33 out of 276,800 alleles). In silico analysis of pathogenicity (through Alamut Visual v2.8.1) is inconclusive regarding this change; PolyPhen2 and MutationTaster predicts it to be likely pathogenic whereas SIFT predicts this variant to be benign. This variant is considered to be a variant of uncertain clinical significance (VOUS) according to the ACMG guidelines.

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