5-112843239-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The NM_000038.6(APC):c.7645C>T(p.Arg2549Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000837 in 1,613,772 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2549H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000038.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APC | NM_000038.6 | c.7645C>T | p.Arg2549Cys | missense_variant | 16/16 | ENST00000257430.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000257430.9 | c.7645C>T | p.Arg2549Cys | missense_variant | 16/16 | 5 | NM_000038.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000176 AC: 44AN: 250674Hom.: 0 AF XY: 0.000221 AC XY: 30AN XY: 135440
GnomAD4 exome AF: 0.0000862 AC: 126AN: 1461532Hom.: 1 Cov.: 34 AF XY: 0.000122 AC XY: 89AN XY: 727096
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74428
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | May 10, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 07, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 20, 2021 | - - |
Familial adenomatous polyposis 1 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Apr 10, 2024 | This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | May 11, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2019 | This variant is associated with the following publications: (PMID: 32369273, 28726808, 26832770) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at