ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.6553C>T (p.Pro2185Ser)

gnomAD frequency: 0.00946  dbSNP: rs77555300
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000226842 SCV000290101 benign Alstrom syndrome 2021-12-18 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 benign Monogenic diabetes 2019-02-15 criteria provided, single submitter research ACMG criteria: BP1 (missense when truncating are ds causing), BA1 (3.4% MAF in gnomAD Africans), BS2 (18 homozygotes in gnomAD), BP4 (REVEL 0.028 + 8 predictors)= Benign (ALMS1 p.P2184S and p.K1810N are likely in LD)
Laboratory for Molecular Medicine,Mass General Brigham 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,; dbSNP rs77555300).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000226842 SCV002506091 benign Alstrom syndrome 2022-02-08 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000429253 SCV002034120 benign not specified no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001795372 SCV002035931 likely benign not provided no assertion criteria provided clinical testing
Natera, Inc. RCV000226842 SCV002082833 benign Alstrom syndrome 2019-12-02 no assertion criteria provided clinical testing

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