12-47077521-C-T

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

2

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]

Genome browser will be placed here

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
AMIGO2NM_001370299.1 linkc.1482G>A p.Glu494Glu synonymous_variant Exon 3 of 3 ENST00000550413.2 NP_001357228.1
AMIGO2NM_001143668.1 linkc.1482G>A p.Glu494Glu synonymous_variant Exon 3 of 3 NP_001137140.1 Q86SJ2A0A024R127
AMIGO2NM_181847.4 linkc.1482G>A p.Glu494Glu synonymous_variant Exon 2 of 2 NP_862830.1 Q86SJ2A0A024R127
AMIGO2XM_047428785.1 linkc.1482G>A p.Glu494Glu synonymous_variant Exon 2 of 2 XP_047284741.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AMIGO2ENST00000550413.2 linkc.1482G>A p.Glu494Glu synonymous_variant Exon 3 of 3 1 NM_001370299.1 ENSP00000449034.1 Q86SJ2
AMIGO2ENST00000266581.4 linkc.1482G>A p.Glu494Glu synonymous_variant Exon 2 of 2 1 ENSP00000266581.4 Q86SJ2
AMIGO2ENST00000429635.1 linkc.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.:
76
Cov.:
33
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.:
19
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.:
81
Cov.:
30
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.:
76
Cov.:
33
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.:
33
Bravo
AF:
0.0202
Asia WGS
AF:
0.00953
AC:
34
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
10
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.

Other links and lift over

dbSNP: rs11836128; hg19: chr12-47471304; COSMIC: COSV99873866; COSMIC: COSV99873866; API