Variant 14-39240565-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000640607.2(MIA2):c.254G>A(p.Gly85Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000678 in 1,608,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

MIA2
ENST00000640607.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.11

Variant links:

Genes affected

MIA2 (HGNC:18432): (MIA SH3 domain ER export factor 2) This gene encodes s receptor in the endoplasmic reticulum, which plays a role in the export of large pre-chylomicrons and pre-very low density lipoproteins (pre-VLDLs). Three major classes of transcripts are generated from this gene- melanoma inhibitory activity 2-specific transcripts, cTAGE family member 5-specific transcripts and transcripts that include exons from both these transcript species (TANGO1-like or TALI). Additionally, alternative splicing in these transcripts results in multiple transcript variants encoding multiple isoforms. [provided by RefSeq, Sep 2016]

MIA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.067840815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIA2	NM_001329214.4 linkuse as main transcript	c.254G>A	p.Gly85Glu	missense_variant	3/29	ENST00000640607.2	NP_001316143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIA2	ENST00000640607.2 linkuse as main transcript	c.254G>A	p.Gly85Glu	missense_variant	3/29	1	NM_001329214.4	ENSP00000491014	P2	Q96PC5-3
MIA2	ENST00000280082.4 linkuse as main transcript	c.254G>A	p.Gly85Glu	missense_variant	3/6	1		ENSP00000280082		Q96PC5-2
MIA2	ENST00000553728.1 linkuse as main transcript	c.254G>A	p.Gly85Glu	missense_variant	3/28	5		ENSP00000452252	A2
MIA2	ENST00000557148.5 linkuse as main transcript	c.254G>A	p.Gly85Glu	missense_variant	5/5	5		ENSP00000451883

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000160

AC:

AN:

250330

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135266

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.000611

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:

0.0000177

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.0000494

AC:

AN:

1456524

Hom.:

Cov.:

AF XY:

0.0000428

AC XY:

AN XY:

724892

show subpopulations

Gnomad4 AFR exome

AF:

0.000540

Gnomad4 AMR exome

AF:

0.000741

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:

0.0000108

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000243

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000718

Hom.:

Bravo

AF:

0.000302

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000189

AC:

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

May 01, 2024

The c.254G>A (p.G85E) alteration is located in exon 3 (coding exon 3) of the MIA2 gene. This alteration results from a G to A substitution at nucleotide position 254, causing the glycine (G) at amino acid position 85 to be replaced by a glutamic acid (E). 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

Pathogenic

0.58

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.093

.;.;.;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.88

D;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.068

T;T;T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Uncertain

2.1

.;.;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-5.5

D;D;D;.

REVEL

Benign

0.13

Sift

Benign

0.21

T;D;T;.

Sift4G

Pathogenic

0.0

D;D;D;.

Polyphen

0.87, 0.89

.;.;P;P

Vest4

0.27, 0.31

MVP

0.54

MPC

0.18

ClinPred

0.10

GERP RS

4.5

Varity_R

0.28

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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