Submissions for variant NM_000053.4(ATP7B):c.3396C>T (p.Ser1132=)

gnomAD frequency: 0.00011  dbSNP: rs370947152

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000395395	SCV000384656	uncertain significance	Wilson disease	2018-01-13	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.
GeneDx	RCV001356076	SCV000528337	likely benign	not provided	2019-12-19	criteria provided, single submitter	clinical testing
Invitae	RCV000395395	SCV001064330	benign	Wilson disease	2024-01-25	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000395395	SCV001977130	likely benign	Wilson disease	2021-08-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002450860	SCV002613173	likely benign	Inborn genetic diseases	2020-02-14	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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	RCV002469127	SCV002766251	likely benign	not specified	2022-11-13	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001356076	SCV003917289	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	ATP7B: BP4, BP7
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356076	SCV001551138	uncertain significance	not provided		no assertion criteria provided	clinical testing	multiple AR variants in same gene - keep for nowA synonymous variant not located in a splice region.1 reputable source/s reports the variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.Allele frequency in the general population is extremely low (0.338%, gnomAD_ExomesFounderPop) with recommended threshold of 0.243% in the general population.3 pathogenic variants with a higher frequency threshold than recommended are known in this gene, including:chr13:52520508:G>A, frequency: 0.243%chr13:52523859:G>A, frequency: 0.235%chr13:52535985:A>C, frequency: 0.232%
Natera, Inc.	RCV000395395	SCV002086811	likely benign	Wilson disease	2020-02-03	no assertion criteria provided	clinical testing