12-47077840-C-T

Variant names:

• chr12-47077840-C-T
• NM_001370299.1:c.1163G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001370299.1(AMIGO2):​c.1163G>A​(p.Ser388Asn) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMIGO2 NM_001370299.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.05

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058525234).
• BP6: Variant 12-47077840-C-T is Benign according to our data. Variant chr12-47077840-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3292881.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMIGO2	NM_001370299.1	c.1163G>A	p.Ser388Asn	missense_variant	Exon 3 of 3	ENST00000550413.2	NP_001357228.1
AMIGO2	NM_001143668.1	c.1163G>A	p.Ser388Asn	missense_variant	Exon 3 of 3		NP_001137140.1
AMIGO2	NM_181847.4	c.1163G>A	p.Ser388Asn	missense_variant	Exon 2 of 2		NP_862830.1
AMIGO2	XM_047428785.1	c.1163G>A	p.Ser388Asn	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.1163G>A	p.Ser388Asn	missense_variant	Exon 3 of 3	1	NM_001370299.1	ENSP00000449034.1
AMIGO2	ENST00000266581.4	c.1163G>A	p.Ser388Asn	missense_variant	Exon 2 of 2	1		ENSP00000266581.4
AMIGO2	ENST00000429635.1	c.1163G>A	p.Ser388Asn	missense_variant	Exon 3 of 3	1		ENSP00000406020.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 15, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Benign	0.063	T;T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.66	.;.;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.090	N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.50	N;N;N
REVEL	Benign	0.070
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.97	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.055
MutPred		0.28		Gain of catalytic residue at R389 (P = 0.003);Gain of catalytic residue at R389 (P = 0.003);Gain of catalytic residue at R389 (P = 0.003);
MVP		0.20
MPC		0.37
ClinPred		0.13	T
GERP RS		0.072
Varity_R		0.039
gMVP		0.17

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: chr12-47471623;