ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.2282+5G>A (rs540145750)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000353496 SCV000374276 uncertain significance Deafness, autosomal recessive 2 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.
Illumina Clinical Services Laboratory,Illumina RCV000268157 SCV000374277 uncertain significance Usher syndrome type 1 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.
Illumina Clinical Services Laboratory,Illumina RCV000304617 SCV000374278 uncertain significance Deafness, autosomal dominant 11 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.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000611667 SCV000711155 uncertain significance not specified 2017-08-03 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The c.2282+5G>A var iant in MYO7A has not been previously reported in individuals with hearing loss, but has been identified in 0.18% (45/24682) of Finnish chromosomes and 0.03% (9 0/260052) of all chromosomes by the Genome Aggregation Database (gnomAD, http:// gnomad.broadinstitute.org; dbSNP rs540145750). Although this variant has been se en in the general population, its frequency is not high enough to rule out a pat hogenic role. This variant is located in the 5' splice region. Computational too ls do not suggest an impact to splicing. However, this information is not predic tive enough to rule out pathogenicity. In summary, while the clinical significan ce of the c.2282+5G>A variant is uncertain, its frequency in the general populat ion suggests that it is more likely to be benign.
Invitae RCV001245741 SCV001419046 uncertain significance not provided 2019-10-15 criteria provided, single submitter clinical testing This sequence change falls in intron 19 of the MYO7A gene. It does not directly change the encoded amino acid sequence of the MYO7A protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs540145750, ExAC 0.1%). This variant has not been reported in the literature in individuals with MYO7A-related disease. ClinVar contains an entry for this variant (Variation ID: 306174). Nucleotide substitutions within 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 may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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