ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.8411G>A (p.Arg2804His)

gnomAD frequency: 0.00057  dbSNP: rs201252809
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000514773 SCV000536368 likely benign not provided 2020-11-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000468894 SCV000541333 likely benign Alstrom syndrome 2025-01-29 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000514773 SCV000610094 uncertain significance not provided 2017-09-05 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000468894 SCV000897045 uncertain significance Alstrom syndrome 2018-10-31 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000468894 SCV001781463 uncertain significance Alstrom syndrome 2021-07-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV002446761 SCV002678338 likely benign Cardiovascular phenotype 2022-08-22 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003114574 SCV003801102 uncertain significance not specified 2023-11-14 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.8408G>A (p.Arg2803His) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00049 in 248568 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in ALMS1 causing Alstrom Syndrome With Dilated Cardiomyopathy (0.00049 vs 0.0018), allowing no conclusion about variant significance. c.8408G>A has been reported in the literature in at least one individual affected with Alstrom Syndrome. This report does not provide unequivocal conclusions about association of the variant with Alstrom Syndrome With Dilated Cardiomyopathy. our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 25846608). Nine submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Multiple submitters reported the variant with conflicting assessments (likely benign n=3, VUS n=6). Based on the evidence outlined above, the variant was classified as uncertain significance.
New York Genome Center RCV000468894 SCV003925078 uncertain significance Alstrom syndrome 2021-10-08 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000514773 SCV004154996 uncertain significance not provided 2023-10-01 criteria provided, single submitter clinical testing ALMS1: PM2, BP4
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000468894 SCV005877176 uncertain significance Alstrom syndrome 2024-10-03 criteria provided, single submitter clinical testing The ALMS1 c.8411G>A; p.Arg2804His variant (rs201252809), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 393018). This variant is found in the non-Finnish European population with an allele frequency of 0.089% (115/128318 alleles, including 1 homozygotes) in the Genome Aggregation Database (v2.1.1). Computational analyses predict that this variant is neutral (REVEL: 0.09). Due to limited information, the clinical significance of this variant is uncertain at this time.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000514773 SCV000924727 uncertain significance not provided 2016-08-16 no assertion criteria provided provider interpretation
Natera, Inc. RCV000468894 SCV001453027 uncertain significance Alstrom syndrome 2020-09-16 no assertion criteria provided clinical testing

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