rs771444735

Variant names:

• chr12-47077622-C-A
• rs771444735
• NM_001370299.1:c.1381G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-47077622-C-A
• chr12-47077622-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370299.1(AMIGO2):​c.1381G>T​(p.Gly461Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G461S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AMIGO2 NM_001370299.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• craniofacial microsomia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2736013).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMIGO2	NM_001370299.1	MANE Select	c.1381G>T	p.Gly461Cys	missense	Exon 3 of 3	NP_001357228.1	Q86SJ2
	AMIGO2	NM_001143668.1		c.1381G>T	p.Gly461Cys	missense	Exon 3 of 3	NP_001137140.1	Q86SJ2
	AMIGO2	NM_181847.4		c.1381G>T	p.Gly461Cys	missense	Exon 2 of 2	NP_862830.1	Q86SJ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMIGO2	ENST00000550413.2	TSL:1 MANE Select	c.1381G>T	p.Gly461Cys	missense	Exon 3 of 3	ENSP00000449034.1	Q86SJ2
	AMIGO2	ENST00000266581.4	TSL:1	c.1381G>T	p.Gly461Cys	missense	Exon 2 of 2	ENSP00000266581.4	Q86SJ2
	AMIGO2	ENST00000429635.1	TSL:1	c.1381G>T	p.Gly461Cys	missense	Exon 3 of 3	ENSP00000406020.1	Q86SJ2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.4
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.099
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.016	D
Polyphen		0.97	D
Vest4		0.28
MutPred		0.33		Gain of catalytic residue at K464 (P = 0.0061)
MVP		0.57
MPC		1.0
ClinPred		0.90	D
GERP RS		4.2
Varity_R		0.27
gMVP		0.16
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs771444735; hg19: chr12-47471405;