Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000865326 | SCV001006272 | likely benign | not provided | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001110583 | SCV001268036 | uncertain significance | Fraser syndrome 2 | 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, 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. |
Ambry Genetics | RCV002536271 | SCV003700954 | uncertain significance | Inborn genetic diseases | 2021-08-13 | criteria provided, single submitter | clinical testing | The c.4960A>C (p.S1654R) alteration is located in exon 1 (coding exon 1) of the FREM2 gene. This alteration results from a A to C substitution at nucleotide position 4960, causing the serine (S) at amino acid position 1654 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Department of Pathology and Laboratory Medicine, |
RCV000865326 | SCV001552425 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The FREM2 p.(Ser1654Arg) variant was not identified in the literature nor was it identified in ClinVar, Cosmic, LOVD 3.0, The variant was also identified in dbSNP (ID: rs114595447). The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The variant occurs outside of the splicing consensus sequence and 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer), SpliceSiteFinder-like and MaxEntScan predict the loss of a 3' splice site a the point of variation. MaxEntScan also predicts a greater than 10% gain in strength of 3' splice site c.4988; although this is not very predictive of pathogenicity. The p.Ser1654 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |