19-1453307-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005883.3(APC2):​c.202G>C​(p.Gly68Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

APC2
NM_005883.3 missense

Scores

5
9
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.87
Variant links:
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
APC2NM_005883.3 linkc.202G>C p.Gly68Arg missense_variant Exon 3 of 15 ENST00000590469.6 NP_005874.1 O95996-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APC2ENST00000590469.6 linkc.202G>C p.Gly68Arg missense_variant Exon 3 of 15 1 NM_005883.3 ENSP00000467073.2 O95996-1A0A0C4DGQ0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.66
BayesDel_addAF
Benign
-0.027
T
BayesDel_noAF
Benign
-0.28
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.46
T;T;T;T;T;.;T
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.91
D;D;D;D;.;D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Uncertain
0.58
D;D;D;D;D;D;D
MetaSVM
Benign
-0.69
T
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-5.3
.;.;.;D;D;.;D
REVEL
Uncertain
0.36
Sift
Pathogenic
0.0
.;.;.;D;D;.;T
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D
Polyphen
1.0
.;.;.;D;D;.;.
Vest4
0.55, 0.77
MutPred
0.43
Gain of MoRF binding (P = 0.0648);Gain of MoRF binding (P = 0.0648);Gain of MoRF binding (P = 0.0648);Gain of MoRF binding (P = 0.0648);Gain of MoRF binding (P = 0.0648);Gain of MoRF binding (P = 0.0648);Gain of MoRF binding (P = 0.0648);
MVP
0.44
MPC
1.7
ClinPred
1.0
D
GERP RS
4.9
Varity_R
0.83
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1199788656; hg19: chr19-1453306; API