14-39237024-C-A

Position:

• chr14-39237024-C-A

Variant summary

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

The ENST00000640607.2(MIA2):​c.218C>A​(p.Ala73Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MIA2 ENST00000640607.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.12

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]

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/exons	MANE	Protein	UniProt
MIA2	NM_001329214.4	c.218C>A	p.Ala73Glu	missense_variant	2/29	ENST00000640607.2	NP_001316143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIA2	ENST00000640607.2	c.218C>A	p.Ala73Glu	missense_variant	2/29	1	NM_001329214.4	ENSP00000491014	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jan 16, 2024

The c.218C>A (p.A73E) alteration is located in exon 2 (coding exon 2) of the MIA2 gene. This alteration results from a C to A substitution at nucleotide position 218, causing the alanine (A) at amino acid position 73 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	Benign	0.31
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.078	.;.;.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Uncertain	-0.0047	T
MutationAssessor	Benign	1.8	.;.;L;L
MutationTaster	Benign	0.61	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.8	D;N;D;.
REVEL	Uncertain	0.53
Sift	Uncertain	0.013	D;D;D;.
Sift4G	Benign	0.075	T;D;D;.
Polyphen		0.96	.;.;D;.
Vest4		0.53, 0.44
MutPred		0.46		Gain of catalytic residue at A73 (P = 0.0265);Gain of catalytic residue at A73 (P = 0.0265);Gain of catalytic residue at A73 (P = 0.0265);Gain of catalytic residue at A73 (P = 0.0265);
MVP		0.91
MPC		0.16
ClinPred		0.95	D
GERP RS		3.4
Varity_R		0.077
gMVP		0.33

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: chr14-39706228;