ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs776572343
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666959 SCV000791336 uncertain significance Wilson disease 2017-05-08 criteria provided, single submitter clinical testing
Invitae RCV000666959 SCV000933934 likely pathogenic Wilson disease 2022-07-22 criteria provided, single submitter clinical testing This variant has been observed in individual(s) with Wilson disease (PMID: 18373411; Invitae). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 551811). This variant is present in population databases (rs776572343, gnomAD 0.003%). This sequence change falls in intron 8 of the ATP7B gene. It does not directly change the encoded amino acid sequence of the ATP7B protein. It affects a nucleotide within the consensus splice site.
Genome-Nilou Lab RCV000666959 SCV001977161 uncertain significance Wilson disease 2021-08-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV002442394 SCV002735651 uncertain significance Inborn genetic diseases 2016-04-08 criteria provided, single submitter clinical testing The c.2355+4A>G intronic variant results from an A to G substitution 4 nucleotides after coding exon 8 in the ATP7B gene. This variant was identified in one individual with biochemical testing suggestive of a diagnosis of Wilson disease; however, additional genotype and phenotype information were not provided (Davies LP, Genet. Test. 2008 Mar; 12(1):139-45). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6109 samples (12218 alleles) with coverage at this position. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.

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