rs377767414
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_020975.6(RET):c.2309G>A(p.Arg770Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R770P) has been classified as Uncertain significance.
Frequency
Consequence
NM_020975.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RET | NM_020975.6 | c.2309G>A | p.Arg770Gln | missense_variant | 13/20 | ENST00000355710.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RET | ENST00000355710.8 | c.2309G>A | p.Arg770Gln | missense_variant | 13/20 | 5 | NM_020975.6 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461778Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3AN XY: 727172
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia, type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has been observed in an individual affected with medullary thyroid carcinoma (PMID: 20013610). ClinVar contains an entry for this variant (Variation ID: 24936). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glutamine at codon 770 of the RET protein (p.Arg770Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at