12-47077895-G-T

Position:

• chr12-47077895-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370299.1(AMIGO2):​c.1108C>A​(p.Arg370Ser) 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. 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. R370H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMIGO2 NM_001370299.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.36

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2274817).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMIGO2	NM_001370299.1	c.1108C>A	p.Arg370Ser	missense_variant	3/3	ENST00000550413.2
AMIGO2	NM_001143668.1	c.1108C>A	p.Arg370Ser	missense_variant	3/3
AMIGO2	NM_181847.4	c.1108C>A	p.Arg370Ser	missense_variant	2/2
AMIGO2	XM_047428785.1	c.1108C>A	p.Arg370Ser	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMIGO2	ENST00000550413.2	c.1108C>A	p.Arg370Ser	missense_variant	3/3	1	NM_001370299.1	P1
AMIGO2	ENST00000266581.4	c.1108C>A	p.Arg370Ser	missense_variant	2/2	1		P1
AMIGO2	ENST00000429635.1	c.1108C>A	p.Arg370Ser	missense_variant	3/3	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.1108C>A (p.R370S) alteration is located in exon 2 (coding exon 1) of the AMIGO2 gene. This alteration results from a C to A substitution at nucleotide position 1108, causing the arginine (R) at amino acid position 370 to be replaced by a serine (S). 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	Uncertain	0.44
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;T;T
Eigen	Benign	-0.0018
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.71	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Uncertain	0.30	D
MutationAssessor	Benign	1.2	L;L;L
MutationTaster	Benign	0.98	D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.44	N;N;N
REVEL	Uncertain	0.40
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.54	T;T;T
Polyphen		0.051	B;B;B
Vest4		0.41
MutPred		0.61		Gain of catalytic residue at Q369 (P = 6e-04);Gain of catalytic residue at Q369 (P = 6e-04);Gain of catalytic residue at Q369 (P = 6e-04);
MVP		0.69
MPC		0.70
ClinPred		0.75	D
GERP RS		4.0
Varity_R		0.13
gMVP		0.57

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

Other links and lift over

dbSNP: rs1001479528; hg19: chr12-47471678;