rs869312785
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_000038.6(APC):c.7235A>G(p.Lys2412Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,514 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K2412E) has been classified as Uncertain significance.
Frequency
Consequence
NM_000038.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APC | NM_000038.6 | c.7235A>G | p.Lys2412Arg | missense_variant | 16/16 | ENST00000257430.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000257430.9 | c.7235A>G | p.Lys2412Arg | missense_variant | 16/16 | 5 | NM_000038.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250006Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135144
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461514Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 8AN XY: 727094
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 2412 of the APC protein (p.Lys2412Arg). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with colon cancer (PMID: 26845104). ClinVar contains an entry for this variant (Variation ID: 224554). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. 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. - |
Uncertain significance, criteria provided, single submitter | research | CSER _CC_NCGL, University of Washington | Mar 11, 2015 | - - |
Colorectal cancer, susceptibility to Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | University of Washington Department of Laboratory Medicine, University of Washington | Nov 20, 2015 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 27, 2022 | The p.K2412R variant (also known as c.7235A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 7235. The lysine at codon 2412 is replaced by arginine, an amino acid with highly similar properties. This variant was detected in a patient with a personal history of colon cancer and less than 5 lifetime cumulative polyps (Shirts BH et al. Genet Med, 2016 Oct;18:974-81). This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. 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