ClinVar Miner

Submissions for variant NM_005476.7(GNE):c.1070+2dup (rs886043636)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000301725 SCV000341224 uncertain significance not provided 2016-04-15 criteria provided, single submitter clinical testing
Invitae RCV000697680 SCV000826305 likely pathogenic GNE myopathy; Sialuria 2018-04-05 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the GNE gene. It does not directly change the encoded amino acid sequence of the GNE protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from likely pathogenic variant in an individual affected with hereditary inclusion-body myopathy (PMID: 15146476, 22231866, Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant has been reported as in combination with another GNE variant in an individual with clinical features suggestive of hereditary inclusion-body myopathy (Invitae). This variant is also known as c.1070+2dupT in the literature. ClinVar contains an entry for this variant (Variation ID: 287448). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this intronic change results in aberrant splicing of GNE primary transcripts (PMID: 15146476). 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.

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