rs1554817823
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_020975.6(RET):c.796G>A(p.Asp266Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RET | NM_020975.6 | c.796G>A | p.Asp266Asn | missense_variant | Exon 4 of 20 | ENST00000355710.8 | NP_066124.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460304Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 726568
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hirschsprung disease, susceptibility to, 1 Uncertain:1
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Multiple endocrine neoplasia, type 2 Uncertain:1
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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 543748). This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 266 of the RET protein (p.Asp266Asn). -
Hereditary cancer-predisposing syndrome Uncertain:1
The p.D266N variant (also known as c.796G>A), located in coding exon 4 of the RET gene, results from a G to A substitution at nucleotide position 796. The aspartic acid at codon 266 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at