Variant 13-25170330-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152704.4(AMER2):c.1290G>C(p.Glu430Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AMER2
NM_152704.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Variant links:

Genes affected

AMER2 (HGNC:26360): (APC membrane recruitment protein 2) Enables phosphatidylinositol-4,5-bisphosphate binding activity. Involved in negative regulation of canonical Wnt signaling pathway. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

AMER2 links:

LINC01053 (HGNC:):

LINC01053 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.0733695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMER2	NM_152704.4 linkuse as main transcript	c.1290G>C	p.Glu430Asp	missense_variant	1/1	ENST00000515384.2	NP_689917.2	Q8N7J2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AMER2	ENST00000515384.2 linkuse as main transcript	c.1290G>C	p.Glu430Asp	missense_variant	1/1	6	NM_152704.4	ENSP00000426528.1	Q8N7J2-1
AMER2	ENST00000357816.2 linkuse as main transcript	c.933G>C	p.Glu311Asp	missense_variant	3/3	2		ENSP00000350469.2	Q8N7J2-2
LINC01053	ENST00000656176.1 linkuse as main transcript	n.63+1299C>G		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250440

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135574

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.1290G>C (p.E430D) alteration is located in exon 1 (coding exon 1) of the AMER2 gene. This alteration results from a G to C substitution at nucleotide position 1290, causing the glutamic acid (E) at amino acid position 430 to be replaced by an aspartic acid (D). 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

0.12

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0075

.;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.073

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.97

N;N

REVEL

Benign

0.022

Sift

Benign

0.35

T;T

Sift4G

Benign

0.55

T;T

Polyphen

0.11

B;B

Vest4

0.12

MutPred

0.42

.;Loss of sheet (P = 0.1158);

MVP

0.030

ClinPred

0.18

GERP RS

3.5

Varity_R

0.20

gMVP

0.051

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over