Submissions for variant NM_139076.3(ABRAXAS1):c.1102_1104del (p.Lys368del)

gnomAD frequency: 0.00001  dbSNP: rs878855206

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000226178	SCV000291352	uncertain significance	not provided	2023-10-17	criteria provided, single submitter	clinical testing	This variant, c.1102_1104del, results in the deletion of 1 amino acid(s) of the ABRAXAS1 protein (p.Lys368del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has been observed in individual(s) with breast cancer (PMID: 29484706). ClinVar contains an entry for this variant (Variation ID: 241853). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003230465	SCV003928693	uncertain significance	not specified	2023-04-10	criteria provided, single submitter	clinical testing	Variant summary: FAM175A c.1102_1104delAAA (p.Lys368del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 8e-06 in 251348 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1102_1104delAAA has been reported in the literature in individuals affected with breast cancer or embryonal tumor. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.