ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.6556C>T (p.Pro2186Ser) (rs77555300)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000226842 SCV000290101 benign Alstrom syndrome 2017-11-13 criteria provided, single submitter clinical testing
GeneDx RCV000429253 SCV000524250 benign not specified 2016-12-05 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.
Personalized Diabetes Medicine Program,University of Maryland School of Medicine RCV000445433 SCV000536980 likely benign Monogenic diabetes 2015-12-22 criteria provided, single submitter research ACMG Criteria: BS2 (ExAC, type2diabetesgenetics.org), BP4
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000429253 SCV000711812 benign not specified 2016-03-21 criteria provided, single submitter clinical testing p.Pro2184Ser in exon 8 of ALMS1: This variant is not expected to have clinical s ignificance because it has been identified in 3.31% (323/9752) of African chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs77555300).
Integrated Genetics/Laboratory Corporation of America RCV000429253 SCV000864116 likely benign not specified 2016-02-15 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.6550C>T (alternative name c.6556C>T) variant affects a non-conserved nucleotide, resulting in amino acid change from Pro to Ser. 4/5 in-silico tools predict this variant to be benign, but these in silico predictions have not been confirmed with functional studies. This variant is found in 355/120368 control chromosomes (6 homozygotes) at a frequency of 0.0029493, with the highest frequency in Africans (0.03312; 5 homozygotes). This African allele frequency significantly exceeds maximal expected frequency of a pathogenic allele (0.0022361), suggesting that this is a benign polymorphism in Africans. Mutations in the ALMS1 gene have been reported with autosomal recessive Alstrom disease (AS), which has estimated prevalence of 1/600,000. 60% of patients with Alstrom syndrome have Dilated Cardiomyopathy (DCM) among other presenting features such as obesity, retinal rod cone dystrophy, diabetes, and progressive hearing loss. This gene was included in Cardio Gene Screening panel based upon the reported findings of DCM in patients with AS. Mutations in ALMS1 gene have not been implicated in isolated cases of cardiomyopathy, which has higher prevalence (1/500), than the AS alone. Taken together, this is probably a normal variant and was classified as likely benign.

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