12-47077840-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001370299.1(AMIGO2):​c.1163G>A​(p.Ser388Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

AMIGO2
NM_001370299.1 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.05
Variant links:
Genes affected
AMIGO2 (HGNC:24073): (adhesion molecule with Ig like domain 2) Predicted to be involved in several processes, including heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; homophilic cell adhesion via plasma membrane adhesion molecules; and negative regulation of programmed cell death. Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be located in nucleus and plasma membrane. Predicted to be integral component of membrane. Biomarker of gastric adenocarcinoma. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.058525234).
BP6
Variant 12-47077840-C-T is Benign according to our data. Variant chr12-47077840-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3292881.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AMIGO2NM_001370299.1 linkc.1163G>A p.Ser388Asn missense_variant Exon 3 of 3 ENST00000550413.2 NP_001357228.1
AMIGO2NM_001143668.1 linkc.1163G>A p.Ser388Asn missense_variant Exon 3 of 3 NP_001137140.1 Q86SJ2A0A024R127
AMIGO2NM_181847.4 linkc.1163G>A p.Ser388Asn missense_variant Exon 2 of 2 NP_862830.1 Q86SJ2A0A024R127
AMIGO2XM_047428785.1 linkc.1163G>A p.Ser388Asn missense_variant Exon 2 of 2 XP_047284741.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AMIGO2ENST00000550413.2 linkc.1163G>A p.Ser388Asn missense_variant Exon 3 of 3 1 NM_001370299.1 ENSP00000449034.1 Q86SJ2
AMIGO2ENST00000266581.4 linkc.1163G>A p.Ser388Asn missense_variant Exon 2 of 2 1 ENSP00000266581.4 Q86SJ2
AMIGO2ENST00000429635.1 linkc.1163G>A p.Ser388Asn missense_variant Exon 3 of 3 1 ENSP00000406020.1 Q86SJ2

Frequencies

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

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 15, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
12
DANN
Benign
0.93
DEOGEN2
Benign
0.063
T;T;T
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.63
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.66
.;.;T
M_CAP
Benign
0.0037
T
MetaRNN
Benign
0.059
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.090
N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
0.50
N;N;N
REVEL
Benign
0.070
Sift
Benign
1.0
T;T;T
Sift4G
Benign
0.97
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.055
MutPred
0.28
Gain of catalytic residue at R389 (P = 0.003);Gain of catalytic residue at R389 (P = 0.003);Gain of catalytic residue at R389 (P = 0.003);
MVP
0.20
MPC
0.37
ClinPred
0.13
T
GERP RS
0.072
Varity_R
0.039
gMVP
0.17

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: chr12-47471623; API