14-47305298-G-T

Position:

• chr14-47305298-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001113498.3(MDGA2):​c.281-3748C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,978 control chromosomes in the GnomAD database, including 4,534 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4534 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MDGA2 NM_001113498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDGA2	NM_001113498.3	c.281-3748C>A		intron_variant		ENST00000399232.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDGA2	ENST00000399232.8	c.281-3748C>A		intron_variant		1	NM_001113498.3	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33125 AN: 151858 Hom.: 4519 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0950

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.181

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.218 AC: 33163 AN: 151978 Hom.: 4534 Cov.: 32 AF XY: 0.212 AC XY: 15716 AN XY: 74280

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.0925

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0950

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.187

Alfa AF: 0.191 Hom.: 525

Bravo AF: 0.231

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	15
DANN	Benign	0.72

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: rs2297926; hg19: chr14-47774501;