12-47077567-T-A

Variant names:

• chr12-47077567-T-A
• NM_001370299.1:c.1436A>T

Variant summary

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

The NM_001370299.1(AMIGO2):​c.1436A>T​(p.Gln479Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AMIGO2 NM_001370299.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.51

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMIGO2	NM_001370299.1	c.1436A>T	p.Gln479Leu	missense_variant	Exon 3 of 3	ENST00000550413.2	NP_001357228.1
AMIGO2	NM_001143668.1	c.1436A>T	p.Gln479Leu	missense_variant	Exon 3 of 3		NP_001137140.1
AMIGO2	NM_181847.4	c.1436A>T	p.Gln479Leu	missense_variant	Exon 2 of 2		NP_862830.1
AMIGO2	XM_047428785.1	c.1436A>T	p.Gln479Leu	missense_variant	Exon 2 of 2		XP_047284741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMIGO2	ENST00000550413.2	c.1436A>T	p.Gln479Leu	missense_variant	Exon 3 of 3	1	NM_001370299.1	ENSP00000449034.1
AMIGO2	ENST00000266581.4	c.1436A>T	p.Gln479Leu	missense_variant	Exon 2 of 2	1		ENSP00000266581.4
AMIGO2	ENST00000429635.1	c.1436A>T	p.Gln479Leu	missense_variant	Exon 3 of 3	1		ENSP00000406020.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1436A>T (p.Q479L) alteration is located in exon 2 (coding exon 1) of the AMIGO2 gene. This alteration results from a A to T substitution at nucleotide position 1436, causing the glutamine (Q) at amino acid position 479 to be replaced by a leucine (L). 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	0.30
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.71	.;.;T
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.9	L;L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.057	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.57
MutPred		0.40		Gain of catalytic residue at K482 (P = 0.0062);Gain of catalytic residue at K482 (P = 0.0062);Gain of catalytic residue at K482 (P = 0.0062);
MVP		0.72
MPC		1.2
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.62
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-47471350;