Submissions for variant NM_015120.4(ALMS1):c.106_108dup (p.Ala36_Asn37insAla)

dbSNP: rs746896173

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000306753	SCV000431903	uncertain significance	Alstrom syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Counsyl	RCV000306753	SCV000790044	uncertain significance	Alstrom syndrome	2017-03-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000306753	SCV000825364	uncertain significance	Alstrom syndrome	2025-02-02	criteria provided, single submitter	clinical testing	This variant, c.106_108dup, results in the insertion of 1 amino acid(s) of the ALMS1 protein (p.Ala36dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs746896173, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 337007). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
GeneDx	RCV001590984	SCV001824947	likely benign	not provided	2020-04-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002402066	SCV002713478	uncertain significance	Cardiovascular phenotype	2023-08-07	criteria provided, single submitter	clinical testing	The c.106_108dupGCG variant (also known as p.A36dup), located in coding exon 1 of the ALMS1 gene, results from an in-frame duplication of GCG at nucleotide positions 106 to 108. This results in the duplication of an extra alanine residue between codons 36 and 37. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Clinical Genomics Laboratory, Stanford Medicine	RCV000306753	SCV005062010	uncertain significance	Alstrom syndrome	2021-07-28	criteria provided, single submitter	clinical testing	The p.Ala36dup variant in the ALMS1gene has not been previously reported in association with disease. This p.Ala36dup varianthas been identified in 11/23,978 Latino/Admixed American chromosomes (22/170,160 chromosomes overall) by the Genome Aggregation Database (http://gnomad.broadinstitute.org/).The p.Ala36dup variant occurs in a repetitive region and the ability to detect this type of variation is limited. Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. The p.Ala36dupvariant results in an in-frame insertion of oneamino acid, and as a result, this variant is not expected to disrupt the protein reading frame. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of thep.Ala36dupvariant is uncertain. Additional information is needed to resolve the significance of this variant.[ACMG evidence codes used: BP3]
PreventionGenetics, part of Exact Sciences	RCV003409538	SCV004108089	uncertain significance	ALMS1-related disorder	2024-06-10	no assertion criteria provided	clinical testing	The ALMS1 c.103_105dupGCG variant is predicted to result in an in-frame duplication (p.Ala35dup). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.046% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.