14-47131743-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001113498.3(MDGA2):c.896T>C(p.Met299Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00357 in 1,580,262 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (85 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (81 hom.)
• Consequence: MDGA2 NM_001113498.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.51

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004794866).
• BP6: Variant 14-47131743-A-G is Benign according to our data. Variant chr14-47131743-A-G is described in ClinVar as [Benign]. Clinvar id is 710031.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA2	NM_001113498.3	c.896T>C	p.Met299Thr	missense_variant	5/17	ENST00000399232.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA2	ENST00000399232.8	c.896T>C	p.Met299Thr	missense_variant	5/17	1	NM_001113498.3	P1

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2889 AN: 151986 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.0667

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00577

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00458 AC: 1137 AN: 248250 Hom.: 29 AF XY: 0.00356 AC XY: 480 AN XY: 134778

Gnomad AFR exome AF: 0.0647

Gnomad AMR exome AF: 0.00317

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000230

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000107

Gnomad OTH exome AF: 0.00166

GnomAD4 exome AF: 0.00193 AC: 2758 AN: 1428158 Hom.: 81 Cov.: 29 AF XY: 0.00167 AC XY: 1185 AN XY: 709136

Gnomad4 AFR exome AF: 0.0680

Gnomad4 AMR exome AF: 0.00344

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.000195

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000441

Gnomad4 OTH exome AF: 0.00473

GnomAD4 genome AF: 0.0190 AC: 2887 AN: 152104 Hom.: 85 Cov.: 32 AF XY: 0.0190 AC XY: 1411 AN XY: 74354

Gnomad4 AFR AF: 0.0665

Gnomad4 AMR AF: 0.00576

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000133

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00309 Hom.: 23

Bravo AF: 0.0211

ESP6500AA AF: 0.0601 AC: 224

ESP6500EA AF: 0.000244 AC: 2

ExAC AF: 0.00562 AC: 679

Asia WGS AF: 0.00318 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	20
Dann	Uncertain	0.98
Eigen	Benign	-0.062
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.59	T;D;T
MetaRNN	Benign	0.0039	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.48	N;N;.
REVEL	Benign	0.15
Sift	Benign	0.69	T;D;.
Polyphen		0.0070	.;.;B
Vest4		0.69
MVP		0.16
ClinPred		0.018	T
GERP RS		5.3
Varity_R		0.16
gMVP		0.37

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: rs73248044; hg19: chr14-47600946;