14-46957472-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001113498.3(MDGA2):​c.1991A>G​(p.Glu664Gly) 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: 32)

Consequence

MDGA2
NM_001113498.3 missense

Scores

2
10
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.44

Publications

0 publications found
Variant links:
Genes affected
MDGA2 (HGNC:19835): (MAM domain containing glycosylphosphatidylinositol anchor 2) Predicted to be involved in regulation of presynapse assembly; regulation of synaptic membrane adhesion; and spinal cord motor neuron differentiation. Predicted to act upstream of or within neuron migration and pattern specification process. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in GABA-ergic synapse and glutamatergic synapse. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
MDGA2NM_001113498.3 linkc.1991A>G p.Glu664Gly missense_variant Exon 9 of 17 ENST00000399232.8 NP_001106970.4 Q7Z553-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MDGA2ENST00000399232.8 linkc.1991A>G p.Glu664Gly missense_variant Exon 9 of 17 1 NM_001113498.3 ENSP00000382178.4 Q7Z553-3
MDGA2ENST00000357362.7 linkc.1097A>G p.Glu366Gly missense_variant Exon 9 of 17 5 ENSP00000349925.3 Q7Z553-2
MDGA2ENST00000557238.5 linkn.*369A>G non_coding_transcript_exon_variant Exon 9 of 14 5 ENSP00000452593.1 G3V5Z1
MDGA2ENST00000557238.5 linkn.*369A>G 3_prime_UTR_variant Exon 9 of 14 5 ENSP00000452593.1 G3V5Z1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
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
Jun 11, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1784A>G (p.K595R) alteration is located in exon 8 (coding exon 8) of the MDGA2 gene. This alteration results from a A to G substitution at nucleotide position 1784, causing the lysine (K) at amino acid position 595 to be replaced by an arginine (R). 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
0.19
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.037
.;.;T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.80
T;T;T
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.52
D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.0
.;.;M
PhyloP100
7.4
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-2.2
N;N;.
REVEL
Uncertain
0.31
Sift
Uncertain
0.0050
D;D;.
Sift4G
Uncertain
0.031
.;D;.
Polyphen
0.79
.;.;P
Vest4
0.74
MutPred
0.34
.;.;Loss of stability (P = 0.0186);
MVP
0.58
MPC
0.32
ClinPred
0.93
D
GERP RS
5.5
Varity_R
0.20
gMVP
0.75
Mutation Taster
=75/25
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.17
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1885606889; hg19: chr14-47426675; API