Submissions for variant NM_000053.4(ATP7B):c.1947-4C>T

gnomAD frequency: 0.00007  dbSNP: rs74904335

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001721333	SCV000529873	likely benign	not provided	2018-09-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000631244	SCV000752268	benign	Wilson disease	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000440735	SCV000918584	uncertain significance	not specified	2017-10-05	criteria provided, single submitter	clinical testing	Variant summary: The ATP7B c.1947-4C>T variant causes a missense change involving the alteration of a non-conserved intronic nucleotide. Mutation taster predicts a damaging 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 159/275932 control chromosomes including two homozygous occurrences (gnomAD), predominantly observed in the East Asian subpopulation at a frequency of 0.008075 (152/18824). This frequency is about 1.5 times the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006), suggesting this is possibly a benign rare polymorphism found primarily in the populations of East Asian origin. Two studies report this variant as a polymorphism, without clearly stating if it was found in WD patients or controls (Kim_1998, Kim_1998). One clinical diagnostic laboratory has classified this variant as likely benign. Taken together, this variant is classified as VUS-possibly benign.
Illumina Laboratory Services, Illumina	RCV000631244	SCV001267852	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.
Genome-Nilou Lab	RCV000631244	SCV001977177	likely benign	Wilson disease	2021-08-10	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000631244	SCV004362492	benign	Wilson disease	2022-09-23	criteria provided, single submitter	clinical testing