Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_000548.5(TSC2):c.504G>T(p.Met168Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,122 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M168V) has been classified as Likely benign.
TSC2 (HGNC:12363): (TSC complex subunit 2) This gene is a tumor suppressor gene that encodes the growth inhibitory protein tuberin. Tuberin interacts with hamartin to form the TSC protein complex which functions in the control of cell growth. This TSC protein complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signaling which is a major regulator of anabolic cell growth. Mutations in this gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. [provided by RefSeq, May 2022]
Verdict is Likely_benign. Variant got -6 ACMG points.
BP6
Variant 16-2055424-G-T is Benign according to our data. Variant chr16-2055424-G-T is described in ClinVar as [Benign]. Clinvar id is 578409.Status of the report is criteria_provided_single_submitter, 1 stars.
Loss of catalytic residue at V164 (P = 0.0151);Loss of catalytic residue at V164 (P = 0.0151);Loss of catalytic residue at V164 (P = 0.0151);.;Loss of catalytic residue at V164 (P = 0.0151);Loss of catalytic residue at V164 (P = 0.0151);Loss of catalytic residue at V164 (P = 0.0151);Loss of catalytic residue at V164 (P = 0.0151);.;Loss of catalytic residue at V164 (P = 0.0151);Loss of catalytic residue at V164 (P = 0.0151);Loss of catalytic residue at V164 (P = 0.0151);Loss of catalytic residue at V164 (P = 0.0151);Loss of catalytic residue at V164 (P = 0.0151);.;