19-1462052-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_005883.3(APC2):c.1728C>T(p.Gly576Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,613,136 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00038 ( 0 hom. )
Consequence
APC2
NM_005883.3 synonymous
NM_005883.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -6.32
Genes affected
APC2 (HGNC:24036): (APC regulator of WNT signaling pathway 2) This gene encodes a strongly conserved protein that has an N-terminal coiled-coil domain followed by an armadillo domain, five 20-amino acid repeats, and two SAMP domains. This protein promotes the assembly of a multiprotein complex that recruits and phosphorylates the Wnt effector beta-catenin and targets beta-catenin for ubiquitylation and proteasomal degradation. This protein therefore plays a role in the reduction of cytoplasmic levels of beta-catenin which in turn reduces activation of Wnt target genes that play a pivotal role in the pathogenesis of various human cancers. The protein encoded by this gene is closely related to the adenomatous polyposis coli (APC) tumor-suppressor protein and has similar tumor-suppressor effects. This gene also plays a role in actin assembly, cell-cell adhesion, and microtubule network formation through its interaction with cytoskeletal proteins. This gene has its highest expression in the central nervous system and is involved in brain development through cytoskeletal regulation in neurons. Alternative splicing produces multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant 19-1462052-C-T is Benign according to our data. Variant chr19-1462052-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 708468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-6.32 with no splicing effect.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APC2 | ENST00000590469.6 | c.1728C>T | p.Gly576Gly | synonymous_variant | Exon 14 of 15 | 1 | NM_005883.3 | ENSP00000467073.2 |
Frequencies
GnomAD3 genomes AF: 0.000388 AC: 59AN: 152152Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000200 AC: 50AN: 250466Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135776
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GnomAD4 exome AF: 0.000376 AC: 550AN: 1460866Hom.: 0 Cov.: 39 AF XY: 0.000355 AC XY: 258AN XY: 726724
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GnomAD4 genome AF: 0.000387 AC: 59AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74454
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Apr 16, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at