17-65537614-ATGGTGGTGG-ATGGTGGTGGTGGTGG
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_004655.4(AXIN2):c.1421_1422insCCACCA(p.His473_His474dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,428,898 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. H474H) has been classified as Likely benign.
Frequency
Consequence
NM_004655.4 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AXIN2 | NM_004655.4 | c.1421_1422insCCACCA | p.His473_His474dup | inframe_insertion | 6/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.1421_1422insCCACCA | p.His473_His474dup | inframe_insertion | 6/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.1421_1422insCCACCA | p.His473_His474dup | inframe_insertion | 5/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.1421_1422insCCACCA | p.His473_His474dup | inframe_insertion | 6/10 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000479 AC: 1AN: 208906Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 112800
GnomAD4 exome AF: 0.0000105 AC: 15AN: 1428898Hom.: 0 Cov.: 37 AF XY: 0.00000986 AC XY: 7AN XY: 709648
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | May 25, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 21, 2022 | The c.1416_1421dupCCACCA (p.H473_H474dup) alteration is located in exon 6 (coding exon 5) of the AXIN2 gene. The alteration consists of an in-frame duplication of 6 nucleotides from position 1416 to 1421, resulting in the duplication of 2 residues. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Oligodontia-cancer predisposition syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | This variant, c.1416_1421dup, results in the insertion of 2 amino acid(s) of the AXIN2 protein (p.His473_His474dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with AXIN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 239988). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 31, 2022 | In-frame insertion of 2 amino acids in a repetitive region with no known function; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15735151) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at