14-47096942-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001113498.3(MDGA2):c.1107C>T(p.Ile369=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00331 in 1,613,310 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (21 hom.)
• Consequence: MDGA2 NM_001113498.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.23

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 14-47096942-G-A is Benign according to our data. Variant chr14-47096942-G-A is described in ClinVar as [Benign]. Clinvar id is 774712.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA2	NM_001113498.3	c.1107C>T	p.Ile369=	synonymous_variant	6/17	ENST00000399232.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA2	ENST00000399232.8	c.1107C>T	p.Ile369=	synonymous_variant	6/17	1	NM_001113498.3	P1

Frequencies

GnomAD3 genomes AF: 0.00266 AC: 404 AN: 151986 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00230

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00706

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00381

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00277 AC: 690 AN: 249030 Hom.: 2 AF XY: 0.00297 AC XY: 401 AN XY: 135086

Gnomad AFR exome AF: 0.000775

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00199

Gnomad FIN exome AF: 0.00589

Gnomad NFE exome AF: 0.00365

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00338 AC: 4932 AN: 1461206 Hom.: 21 Cov.: 32 AF XY: 0.00331 AC XY: 2407 AN XY: 726926

Gnomad4 AFR exome AF: 0.000598

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00206

Gnomad4 FIN exome AF: 0.00556

Gnomad4 NFE exome AF: 0.00374

Gnomad4 OTH exome AF: 0.00292

GnomAD4 genome AF: 0.00266 AC: 405 AN: 152104 Hom.: 1 Cov.: 32 AF XY: 0.00295 AC XY: 219 AN XY: 74362

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.00230

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.00706

Gnomad4 NFE AF: 0.00381

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00331 Hom.: 0

Bravo AF: 0.00244

Asia WGS AF: 0.00115 AC: 4 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

Aug 04, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	11
Dann	Benign	0.78

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: rs200459170; hg19: chr14-47566145;