ClinVar

Description

The ATM c.7928-10T>C variant was not identified in the literature. The variant was identified in dbSNP (ID: rs188404773) as "With Uncertain significance allele", ClinVar (classified as benign by Invitae, as likely benign by EGL Genetic Diagnostics, and as uncertain significance by GeneDx, University of Chicago and Integrated Genetics), and in LOVD 3.0 (classified as likely benign by VKGL data sharing initiative).The variant was identified in control databases in 60 of 276948 chromosomes at a frequency of 0.0002 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 56 of 24028 chromosomes (freq: 0.002), Other in 1 of 6460 chromosomes (freq: 0.00016), Latino in 2 of 34418 chromosomes (freq: 0.00006), European Non-Finnish in 1 of 126484 chromosomes (freq: 0.000008), while the variant was not observed in the Ashkenazi Jewish, East Asian, European Finnish, and South Asian populations. The ATM c.7928-10T>C variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. In addition, 0 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% 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.