Submissions for variant NM_001378454.1(ALMS1):c.6458A>G (p.Gln2153Arg)

gnomAD frequency: 0.00004  dbSNP: rs534635095

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000408035	SCV000431922	uncertain significance	Alstrom syndrome	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001699377	SCV001993036	uncertain significance	not provided	2019-07-03	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000408035	SCV002304621	uncertain significance	Alstrom syndrome	2025-01-06	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 2154 of the ALMS1 protein (p.Gln2154Arg). This variant is present in population databases (rs534635095, gnomAD 0.007%). This missense change has been observed in individual(s) with focal segmental glomerulosclerosis (PMID: 31308072). This variant is also known as c.6455A>G (p.Gln2152Arg). ClinVar contains an entry for this variant (Variation ID: 337021). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Clinical Genetics, Academic Medical Center	RCV001699377	SCV001923286	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001699377	SCV001927011	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001699377	SCV001970382	likely benign	not provided		no assertion criteria provided	clinical testing