Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_020975.6(RET):c.2598C>A(p.Ala866Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A866A) has been classified as Likely benign.
RET (HGNC:9967): (ret proto-oncogene) This gene encodes a transmembrane receptor and member of the tyrosine protein kinase family of proteins. Binding of ligands such as GDNF (glial cell-line derived neurotrophic factor) and other related proteins to the encoded receptor stimulates receptor dimerization and activation of downstream signaling pathways that play a role in cell differentiation, growth, migration and survival. The encoded receptor is important in development of the nervous system, and the development of organs and tissues derived from the neural crest. This proto-oncogene can undergo oncogenic activation through both cytogenetic rearrangement and activating point mutations. Mutations in this gene are associated with Hirschsprung disease and central hypoventilation syndrome and have been identified in patients with renal agenesis. [provided by RefSeq, Sep 2017]
RET Gene-Disease associations (from GenCC):
familial medullary thyroid carcinoma
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
multiple endocrine neoplasia type 2A
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant 10-43119736-C-A is Benign according to our data. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-43119736-C-A is described in CliVar as Likely_benign. Clinvar id is 3660045.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-3.05 with no splicing effect.