rs200459170

Variant names:

• chr14-47096942-G-A
• rs200459170
• NM_001113498.3:c.1107C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-47096942-G-A
• chr14-47096942-G-C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The NM_001113498.3(MDGA2):​c.1107C>T​(p.Ile369Ile) 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
• Publications: 3 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.186).
• BP6: Variant 14-47096942-G-A is Benign according to our data. Variant chr14-47096942-G-A is described in ClinVar as Benign. ClinVar VariationId is 774712.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 21 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113498.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	NM_001113498.3	MANE Select	c.1107C>T	p.Ile369Ile	synonymous	Exon 6 of 17	NP_001106970.4	Q7Z553-3
	MDGA2	NM_182830.4		c.213C>T	p.Ile71Ile	synonymous	Exon 6 of 17	NP_878250.2	Q7Z553-2
	MDGA2	NR_103766.2		n.971C>T		non_coding_transcript_exon	Exon 6 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	ENST00000399232.8	TSL:1 MANE Select	c.1107C>T	p.Ile369Ile	synonymous	Exon 6 of 17	ENSP00000382178.4	Q7Z553-3
	MDGA2	ENST00000357362.7	TSL:5	c.213C>T	p.Ile71Ile	synonymous	Exon 6 of 17	ENSP00000349925.3	Q7Z553-2
	MDGA2	ENST00000554762.5	TSL:3	c.222C>T	p.Ile74Ile	synonymous	Exon 2 of 4	ENSP00000450827.1	H0YJ52

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

GnomAD2 exomes AF: 0.00277 AC: 690 AN: 249030 AF XY: 0.00297

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 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

African (AFR) AF: 0.000598 AC: 20 AN: 33450

American (AMR) AF: 0.00181 AC: 81 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.000383 AC: 10 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00206 AC: 178 AN: 86246

European-Finnish (FIN) AF: 0.00556 AC: 297 AN: 53416

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5766

European-Non Finnish (NFE) AF: 0.00374 AC: 4153 AN: 1111510

Other (OTH) AF: 0.00292 AC: 176 AN: 60364

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

African (AFR) AF: 0.000433 AC: 18 AN: 41538

American (AMR) AF: 0.00230 AC: 35 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4820

European-Finnish (FIN) AF: 0.00706 AC: 75 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00381 AC: 259 AN: 67940

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.00317 Hom.: 0

Bravo AF: 0.00244

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		6.2
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs200459170; hg19: chr14-47566145; COSMIC: COSV107420609;