rs1554087876

Variant summary

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

The NM_000038.6(APC):​c.6954T>A​(p.Ser2318Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2318G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

APC
NM_000038.6 missense

Scores

1
10
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.973
Variant links:
Genes affected
APC (HGNC:583): (APC regulator of WNT signaling pathway) This gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It is also involved in other processes including cell migration and adhesion, transcriptional activation, and apoptosis. Defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Mutations in the APC gene have been found to occur in most colorectal cancers, where disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. [provided by RefSeq, Jun 2022]

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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/exons MANE UniProt
APCNM_000038.6 linkuse as main transcriptc.6954T>A p.Ser2318Arg missense_variant 16/16 ENST00000257430.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
APCENST00000257430.9 linkuse as main transcriptc.6954T>A p.Ser2318Arg missense_variant 16/165 NM_000038.6 P1P25054-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.93
BayesDel_addAF
Uncertain
0.073
D
BayesDel_noAF
Benign
-0.13
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.35
T;T
Eigen
Benign
-0.011
Eigen_PC
Benign
-0.013
FATHMM_MKL
Benign
0.69
D
LIST_S2
Uncertain
0.94
.;D
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.45
T;T
MetaSVM
Uncertain
-0.13
T
MutationAssessor
Benign
1.6
L;L
MutationTaster
Benign
0.89
D;D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.86
N;N
REVEL
Uncertain
0.53
Sift
Uncertain
0.020
D;D
Sift4G
Uncertain
0.056
T;T
Polyphen
0.90
P;P
Vest4
0.49
MutPred
0.39
Loss of phosphorylation at S2318 (P = 0.0059);Loss of phosphorylation at S2318 (P = 0.0059);
MVP
0.84
ClinPred
0.74
D
GERP RS
2.3
Varity_R
0.13
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-112178245; API