Submissions for variant NM_001378454.1(ALMS1):c.6302C>A (p.Ser2101Ter)

dbSNP: rs28730854

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV001091888	SCV001248155	pathogenic	not provided	2018-07-01	criteria provided, single submitter	clinical testing
Invitae	RCV001230120	SCV001402590	pathogenic	Alstrom syndrome	2023-12-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser2102*) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). This variant is present in population databases (rs28730854, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with Alstrom syndrome (PMID: 17594715, 30488743). ClinVar contains an entry for this variant (Variation ID: 871762). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV001266523	SCV001444698	pathogenic	Inborn genetic diseases	2020-01-08	criteria provided, single submitter	clinical testing
GeneDx	RCV001091888	SCV001770596	pathogenic	not provided	2020-06-25	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 17594715, 31106028, 29302074, 30488743, 30064963)
DASA	RCV001230120	SCV002499424	pathogenic	Alstrom syndrome	2022-04-10	criteria provided, single submitter	clinical testing	The c.6305C>A;p.(Ser2102*) variant creates a premature translational stop signal in the ALMS1 gene. It is expected to result in an absent or disrupted protein product -PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 871762; PMID: 30488743; 30064963; 17594715) - PS4. The variant is present at low allele frequencies population databases (rs28730854 – gnomAD 0.0004602%; ABraOM no frequency - https://abraom.ib.usp.br/) - PM2_supporting. The p.(Ser2102*) was detected in trans with a pathogenic variant (PMID: 30488743; 30064963; 17594715) - PM3. In summary, the currently available evidence indicates that the variant is pathogenic.
Ambry Genetics	RCV002365792	SCV002660575	pathogenic	Cardiovascular phenotype	2021-01-11	criteria provided, single submitter	clinical testing	The p.S2102* pathogenic mutation (also known as c.6305C>A), located in coding exon 8 of the ALMS1 gene, results from a C to A substitution at nucleotide position 6305. This changes the amino acid from a serine to a stop codon within coding exon 8. This mutation has been reported in the compound heterozygous state with other alterations which are expected to be pathogenic or likely pathogenic in several individuals with Alstrom syndrome or related features (Marshall JD et al. Hum Mutat, 2007 Nov;28:1114-23; Citton V et al. J Neuroradiol, 2016 Jun;43:195-9; Han JC et al. J Clin Endocrinol Metab, 2018 07;103:2707-2719; Hu H et al. Mol Psychiatry, 2019 07;24:1027-1039; Wang P et al. Transl Vis Sci Technol, 2019 Mar;8:21). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Fulgent Genetics, Fulgent Genetics	RCV001230120	SCV002799605	pathogenic	Alstrom syndrome	2021-10-26	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001230120	SCV003835053	pathogenic	Alstrom syndrome	2021-06-01	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001230120	SCV002082825	pathogenic	Alstrom syndrome	2021-08-19	no assertion criteria provided	clinical testing