Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute for Clinical Genetics, |
RCV001357963 | SCV002011249 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001357963 | SCV001553577 | likely benign | not provided | no assertion criteria provided | clinical testing | The ATN1 p.Gln498_Gln502del variant was not identified in the literature nor was it identified in the MutDB or LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs377147612), ClinVar and Cosmic. The variant was identified in control databases in 41 of 259998 chromosomes at a frequency of 0.000158 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 19 of 20928 chromosomes (freq: 0.000908), Other in 2 of 6794 chromosomes (freq: 0.000294), Latino in 9 of 31612 chromosomes (freq: 0.000285), East Asian in 3 of 16812 chromosomes (freq: 0.000178) and European (non-Finnish) in 8 of 122724 chromosomes (freq: 0.000065), while the variant was not observed in the Ashkenazi Jewish, European (Finnish) and South Asian populations. This variant is an in-frame deletion resulting in the removal of 5 glutamine (gln) residues at codon 498, within a glutamine repeat region. The insertion of (CAG)n or glutamine repeats has been found to cause dentatorubro-pallidoluysian atrophy, however this variant is a (CAG)n repeat deletion within the normal range of 6-35 repeats (Koide_1994_PMID: 8136840; MIM: 607462). The impact of this alteration on ATN1 protein function is not known, however MutationTaster predicts this variant to be a polymorphism. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |