Genetic Variant AMIGO2:p.Asn328Asp (chr12-47078021-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001370299.1(AMIGO2):c.982A>G(p.Asn328Asp) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N328S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

AMIGO2
NM_001370299.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

Publications

0 publications found

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]

AMIGO2 links:

PCED1B (HGNC:28255): (PC-esterase domain containing 1B) This gene encodes a protein that belongs to the GDSL/SGNH-like acyl-esterase family. Members of this family are hydrolases thought to function in modification of biopolymers on the cell surface. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

PCED1B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12727308).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370299.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMIGO2	NM_001370299.1	MANE Select	c.982A>G	p.Asn328Asp	missense	Exon 3 of 3	NP_001357228.1	Q86SJ2
AMIGO2	NM_001143668.1		c.982A>G	p.Asn328Asp	missense	Exon 3 of 3	NP_001137140.1	Q86SJ2
AMIGO2	NM_181847.4		c.982A>G	p.Asn328Asp	missense	Exon 2 of 2	NP_862830.1	Q86SJ2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMIGO2	ENST00000550413.2	TSL:1 MANE Select	c.982A>G	p.Asn328Asp	missense	Exon 3 of 3	ENSP00000449034.1	Q86SJ2
AMIGO2	ENST00000266581.4	TSL:1	c.982A>G	p.Asn328Asp	missense	Exon 2 of 2	ENSP00000266581.4	Q86SJ2
AMIGO2	ENST00000429635.1	TSL:1	c.982A>G	p.Asn328Asp	missense	Exon 3 of 3	ENSP00000406020.1	Q86SJ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

Eigen

Benign

-0.12

Eigen_PC

Benign

0.032

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.81

M_CAP

Benign

0.073

MetaRNN

Benign

0.13

MetaSVM

Uncertain

0.24

MutationAssessor

Benign

1.8

PhyloP100

2.2

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.33

Sift

Benign

0.035

Sift4G

Benign

0.21

Polyphen

0.13

Vest4

0.15

MutPred

0.49

Gain of catalytic residue at P326 (P = 0.0027)

MVP

0.77

MPC

0.92

ClinPred

0.81

GERP RS

4.0

Varity_R

0.28

gMVP

0.26

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over