Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001082105 | SCV000290072 | benign | Alstrom syndrome | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Center for Pediatric Genomic Medicine, |
RCV000435494 | SCV000510969 | likely benign | not provided | 2016-09-12 | criteria provided, single submitter | clinical testing | Converted during submission to Likely benign. |
Gene |
RCV000434450 | SCV000528959 | likely benign | not specified | 2018-01-02 | 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. |
Genetic Services Laboratory, |
RCV000434450 | SCV000593109 | likely benign | not specified | 2016-12-30 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000434450 | SCV000864106 | benign | not specified | 2018-05-21 | criteria provided, single submitter | clinical testing | Variant summary: ALMS1 c.1267G>A (p.Val423Ile, alternative name c.1270G>A) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0028 in 276990 control chromosomes, predominantly found within the South Asian subpopulation with a frequency of 0.0051 in the gnomAD database, including 4 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 2.3 fold of the estimated maximal expected allele frequency for a pathogenic variant in ALMS1 causing Cardiomyopathy phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. At least one publication reports experimental evidence, demonstrating no sign of exon skipping with normal ALMS1 expression and without discernible defects in ciliary morphology in a cell line established from an individual carrying the variant (Chen 2017). These results indicate no damaging effect for this variant. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. |
Laboratory for Molecular Medicine, |
RCV000434450 | SCV000967143 | likely benign | not specified | 2016-03-21 | criteria provided, single submitter | clinical testing | p.Val423Ile in exon 6 of ALMS1: This variant is not expected to have clinical si gnificance because it has been identified in 0.50% (82/16512) of South Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs45630557). |
Athena Diagnostics Inc | RCV000435494 | SCV001142998 | benign | not provided | 2018-09-20 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000435494 | SCV001152347 | likely benign | not provided | 2019-08-01 | criteria provided, single submitter | clinical testing | |
Personalized Diabetes Medicine Program, |
RCV001172509 | SCV001335562 | likely benign | Monogenic diabetes | 2017-03-31 | criteria provided, single submitter | research | ACMG criteria: BP4 (9 predictors), BP1 (missense when truncating cause disease)=likely benign |