ClinVar

Description

The ALK p.Glu1435del variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs138827116) and in ClinVar (classified as likely benign by EGL Genetics and Illumina and as benign by Invitae). The variant was identified in control databases in 488 of 266110 chromosomes (4 homozygous) at a frequency of 0.001834 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 456 of 24732 chromosomes (freq: 0.01844), Other in 4 of 6686 chromosomes (freq: 0.000598), Latino in 18 of 33230 chromosomes (freq: 0.000542), Ashkenazi Jewish in 2 of 8558 chromosomes (freq: 0.000234), European (non-Finnish) in 7 of 122668 chromosomes (freq: 0.000057) and South Asian in 1 of 26748 chromosomes (freq: 0.000037); it was not observed in the East Asian and European (Finnish) populations. This variant is an in-frame deletion resulting in the removal of a glutamic acid (Glu) residue at codon 1435; the impact of this alteration on ALK protein function is not known. 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.