rs73248044

Variant names:

• chr14-47131743-A-C
• rs73248044
• NM_001113498.3:c.896T>G

Your query was ambiguous. Multiple possible variants found:

• chr14-47131743-A-C
• chr14-47131743-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001113498.3(MDGA2):​c.896T>G​(p.Met299Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M299T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MDGA2 NM_001113498.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.51
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39242083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.896T>G	p.Met299Arg	missense_variant	Exon 5 of 17	ENST00000399232.8	NP_001106970.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.896T>G	p.Met299Arg	missense_variant	Exon 5 of 17	1	NM_001113498.3	ENSP00000382178.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	.;.;T
Eigen	Benign	-0.030
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.69	T;D;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.69	.;.;N
PhyloP100		4.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.1	N;N;.
REVEL	Benign	0.20
Sift	Benign	0.58	T;D;.
Sift4G	Uncertain	0.0070	.;D;.
Polyphen		0.070	.;.;B
Vest4		0.68
MutPred		0.51		.;.;Gain of catalytic residue at N225 (P = 0.0022);
MVP		0.40
ClinPred		0.88	D
GERP RS		5.3
PromoterAI		-0.033	Neutral
Varity_R		0.59
gMVP		0.60
Mutation Taster		=139/61	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs73248044; hg19: chr14-47600946;