Genetic Variant AMIGO2:p.Glu494Glu (chr12-47077521-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001370299.1(AMIGO2):c.1482G>A(p.Glu494Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,614,150 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 76 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 81 hom. )

Consequence

AMIGO2
NM_001370299.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.46

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 12-47077521-C-T is Benign according to our data. Variant chr12-47077521-C-T is described in ClinVar as [Benign]. Clinvar id is 779523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMIGO2	NM_001370299.1 link	c.1482G>A	p.Glu494Glu	synonymous_variant	Exon 3 of 3	ENST00000550413.2	NP_001357228.1
AMIGO2	NM_001143668.1 link	c.1482G>A	p.Glu494Glu	synonymous_variant	Exon 3 of 3		NP_001137140.1	Q86SJ2A0A024R127
AMIGO2	NM_181847.4 link	c.1482G>A	p.Glu494Glu	synonymous_variant	Exon 2 of 2		NP_862830.1	Q86SJ2A0A024R127
AMIGO2	XM_047428785.1 link	c.1482G>A	p.Glu494Glu	synonymous_variant	Exon 2 of 2		XP_047284741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AMIGO2	ENST00000550413.2 link	c.1482G>A	p.Glu494Glu	synonymous_variant	Exon 3 of 3	1	NM_001370299.1	ENSP00000449034.1	Q86SJ2
AMIGO2	ENST00000266581.4 link	c.1482G>A	p.Glu494Glu	synonymous_variant	Exon 2 of 2	1		ENSP00000266581.4	Q86SJ2
AMIGO2	ENST00000429635.1 link	c.1482G>A	p.Glu494Glu	synonymous_variant	Exon 3 of 3	1		ENSP00000406020.1	Q86SJ2

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2632

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0581

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.00472

AC:

1187

AN:

251344

Hom.:

AF XY:

0.00361

AC XY:

490

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.0582

Gnomad AMR exome

AF:

0.00396

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000748

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00230

AC:

3357

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

1489

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0600

Gnomad4 AMR exome

AF:

0.00458

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000623

Gnomad4 OTH exome

AF:

0.00621

GnomAD4 genome

AF:

0.0173

AC:

2637

AN:

152288

Hom.:

Cov.:

AF XY:

0.0169

AC XY:

1262

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0581

Gnomad4 AMR

AF:

0.00909

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.0171

Alfa

AF:

0.00978

Hom.:

Bravo

AF:

0.0202

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.86

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