Variant 12-47078174-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001370299.1(AMIGO2):c.829G>A(p.Asp277Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,614,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

AMIGO2
NM_001370299.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.84

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04520166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AMIGO2	NM_001370299.1 linkuse as main transcript	c.829G>A	p.Asp277Asn	missense_variant	3/3	ENST00000550413.2
AMIGO2	NM_001143668.1 linkuse as main transcript	c.829G>A	p.Asp277Asn	missense_variant	3/3
AMIGO2	NM_181847.4 linkuse as main transcript	c.829G>A	p.Asp277Asn	missense_variant	2/2
AMIGO2	XM_047428785.1 linkuse as main transcript	c.829G>A	p.Asp277Asn	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
AMIGO2	ENST00000550413.2 linkuse as main transcript	c.829G>A	p.Asp277Asn	missense_variant	3/3	1	NM_001370299.1	P1
AMIGO2	ENST00000266581.4 linkuse as main transcript	c.829G>A	p.Asp277Asn	missense_variant	2/2	1		P1
AMIGO2	ENST00000429635.1 linkuse as main transcript	c.829G>A	p.Asp277Asn	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000131

AC:

AN:

251462

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000211

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000132

AC:

193

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

112

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000139

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000125

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.000113

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.829G>A (p.D277N) alteration is located in exon 2 (coding exon 1) of the AMIGO2 gene. This alteration results from a G to A substitution at nucleotide position 829, causing the aspartic acid (D) at amino acid position 277 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.029

T;T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.091

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.0088

MetaRNN

Benign

0.045

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;L

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.42

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.51

T;T;T

Sift4G

Benign

0.41

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.13

MVP

0.54

MPC

0.40

ClinPred

0.040

GERP RS

3.8

Varity_R

0.11

gMVP

0.67

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over