Submissions for variant NM_000053.4(ATP7B):c.2355+13T>G

gnomAD frequency: 0.00293  dbSNP: rs139211339

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000145262	SCV000192327	benign	not specified	2013-02-08	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000145262	SCV000301702	likely benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000145262	SCV000525798	likely benign	not specified	2018-01-03	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586589	SCV000694421	benign	not provided	2016-11-17	criteria provided, single submitter	clinical testing	Variant summary: The ATP7B c.2355+13T>G variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 357/119646 control chromosomes (1 homozygote), predominantly observed in the European (Finnish) subpopulation at a frequency of 0.0062046 (41/6608). This frequency is about the same frequency as the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006), suggesting this is likely a benign polymorphism found primarily in the populations of European (Finnish) origin. The variant has been reported in the literature without strong evidence for causality, and in one case was present on the same chromosome as a known pathogenic variant, supporting the benign role of the variant. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000607602	SCV001005544	benign	Wilson disease	2024-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000586589	SCV001150657	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	ATP7B: BS2
Illumina Laboratory Services, Illumina	RCV000607602	SCV001272331	uncertain significance	Wilson disease	2019-05-02	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000607602	SCV001477663	benign	Wilson disease	2020-08-21	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000607602	SCV000733361	likely benign	Wilson disease		no assertion criteria provided	clinical testing
GenomeConnect, ClinGen	RCV000586589	SCV001423299	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Likely benign and reported on 09-19-2018 by Lab or GTR ID 239772. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Natera, Inc.	RCV000607602	SCV001456178	likely benign	Wilson disease	2020-04-15	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000145262	SCV001808098	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000145262	SCV001920730	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000145262	SCV001928206	benign	not specified		no assertion criteria provided	clinical testing