ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3077+5G>A (rs777003996)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000583449 SCV000687446 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-05 criteria provided, single submitter clinical testing
GeneDx RCV000480882 SCV000567013 uncertain significance not provided 2017-08-15 criteria provided, single submitter clinical testing This variant is denoted ATM c.3077+5G>A or IVS20+5G>A and consists of a G>A nucleotide substitution at the +5 position of intron 20 of the ATM gene. Multiple in silico models predict this variant to damage the nearby natural donor site, and to possibly cause abnormal gene splicing; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM c.3077+5G>A was not observed at a significant frequency in large population cohorts (Lek 2016, The 1000 Genomes Consortium 2015, NHLBI Exome Sequencing Project). The guanine (G) nucleotide that is altered is conserved across species. Based on currently available information, it is unclear whether ATM c.3077+5G>A is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000804209 SCV000944105 uncertain significance Ataxia-telangiectasia syndrome 2018-10-23 criteria provided, single submitter clinical testing This sequence change falls in intron 20 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs777003996, ExAC 0.02%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 419299). 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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