NM_001113498.3:c.3056C>G

Variant names:

• chr14-46841953-G-C
• rs1880630939
• NM_001113498.3:c.3056C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001113498.3(MDGA2):​c.3056C>G​(p.Ser1019Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MDGA2 NM_001113498.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54

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

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=0.21011081).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.3056C>G	p.Ser1019Cys	missense_variant	Exon 17 of 17	ENST00000399232.8	NP_001106970.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.3056C>G	p.Ser1019Cys	missense_variant	Exon 17 of 17	1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000357362.7	c.2162C>G	p.Ser721Cys	missense_variant	Exon 17 of 17	5		ENSP00000349925.3

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	0.075
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.032	.;.;T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.55	.;.;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.3	N;N;.
REVEL	Benign	0.11
Sift	Uncertain	0.015	D;D;.
Sift4G	Benign	0.12	.;T;.
Polyphen		0.55	.;.;P
Vest4		0.27
MutPred		0.39		.;.;Gain of catalytic residue at V947 (P = 0.0013);
MVP		0.59
MPC		0.14
ClinPred		0.68	D
GERP RS		6.0
Varity_R		0.12
gMVP		0.87

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

Other links and lift over

dbSNP: rs1880630939; hg19: chr14-47311156;