Submissions for variant NM_018075.5(ANO10):c.980A>G (p.Tyr327Cys)

gnomAD frequency: 0.00359  dbSNP: rs146569520

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000613613	SCV000444335	uncertain significance	Autosomal recessive spinocerebellar ataxia 10	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000415975	SCV000493216	likely benign	not provided	2024-11-01	criteria provided, single submitter	clinical testing	ANO10: BS2
GeneDx	RCV000415975	SCV000529825	uncertain significance	not provided	2016-07-13	criteria provided, single submitter	clinical testing	The Y327C variant in the ANO10 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports Y327C was observed in 60/8600 (0.7%) alleles from individuals of European American background, indicating it may be a rare variant in this population. The Y327C variant is a non-conservative amino acid substitution, which occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret Y327C as a variant of uncertain significance.
Athena Diagnostics	RCV000415975	SCV000612354	likely benign	not provided	2020-06-15	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000613613	SCV000744191	likely benign	Autosomal recessive spinocerebellar ataxia 10	2016-09-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000415975	SCV001110581	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002520121	SCV003594368	uncertain significance	Inborn genetic diseases	2021-06-11	criteria provided, single submitter	clinical testing	The c.980A>G (p.Y327C) alteration is located in exon 6 (coding exon 5) of the ANO10 gene. This alteration results from a A to G substitution at nucleotide position 980, causing the tyrosine (Y) at amino acid position 327 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic	RCV000415975	SCV004226097	uncertain significance	not provided	2023-02-03	criteria provided, single submitter	clinical testing	BS1
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000613613	SCV000734281	likely benign	Autosomal recessive spinocerebellar ataxia 10		no assertion criteria provided	clinical testing