Description
The ATM p.Phe662= variant was identified in 2 of 348 proband chromosomes (frequency: 0.006) from Swedish and Canadian individuals or families with breast cancer (and a family history of tumours associated with AT) and non-Hodgkin lymphoma, and was not identified in 126 control chromosomes from healthy individuals (Vorechovsky_1996_ 8797579, Sipahimalani_2007_17640065). The variant was also found in 2 cell lines derived from non-lymphoid malignancies (Ejima_2000_ 10738255). The variant was identified in dbSNP (ID: rs1800055) “With Likely benign allele”, ClinVar (classified benign by GeneDx, and likely benign by Invitae, Ambry Genetics, Color Genomics Inc and ARUP), Clinvitae (3x), and was not identified in Cosmic, MutDB, LOVD 3.0, or ATM-LOVD. The variant was also identified in control databases in 133 of 277116 chromosomes at a frequency of 0.0005 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Observation by population include: African in 2 of 24036 chromosomes (freq: 0.00008), “Other” in 3 of 6460 chromosomes (freq: 0.0005), Latino in 10 of 34418 chromosomes (freq: 0.0003), European Non-Finnish in 105 of 126626 chromosomes (freq: 0.0008), Ashkenazi Jewish in 11 of 10148 chromosomes (freq: 0.001), and European Finnish in 2 of 25782 chromosomes (freq: 0.00008); it was not observed in the East Asian and South Asian populations. The p.Phe662= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. 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.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | unknown | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |