chr10-43077222-G-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_020975.6(RET):c.-37G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000115 in 1,474,730 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 35)
Exomes 𝑓: 0.0000083 ( 0 hom. )
Consequence
RET
NM_020975.6 5_prime_UTR
NM_020975.6 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0820
Genes affected
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 10-43077222-G-C is Benign according to our data. Variant chr10-43077222-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 477374.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RET | NM_020975.6 | c.-37G>C | 5_prime_UTR_variant | 1/20 | ENST00000355710.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RET | ENST00000355710.8 | c.-37G>C | 5_prime_UTR_variant | 1/20 | 5 | NM_020975.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151978Hom.: 0 Cov.: 35
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GnomAD3 exomes AF: 0.0000339 AC: 3AN: 88482Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 49940
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GnomAD4 exome AF: 0.00000832 AC: 11AN: 1322752Hom.: 0 Cov.: 30 AF XY: 0.00000307 AC XY: 2AN XY: 650982
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Multiple endocrine neoplasia, type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 19, 2022 | This variant occurs in a non-coding region of the RET gene. It does not change the encoded amino acid sequence of the RET protein. This variant is present in population databases (rs751005619, gnomAD 0.07%). This variant has been observed in individual(s) with Hirschsprung disease (PMID: 14633923). ClinVar contains an entry for this variant (Variation ID: 477374). 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 23, 2018 | See Variant Classification Assertion Criteria. - |
Computational scores
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BayesDel_noAF
Benign
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Dann
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at