chr14-47144184-A-G

Variant names:

• chr14-47144184-A-G
• NM_001113498.3:c.686T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182830.4(MDGA2):​c.-209T>C variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MDGA2 NM_182830.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.86
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22280991).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182830.4. 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.686T>C	p.Val229Ala	missense	Exon 4 of 17	NP_001106970.4	Q7Z553-3
	MDGA2	NM_182830.4		c.-209T>C		5_prime_UTR_premature_start_codon_gain	Exon 4 of 17	NP_878250.2	Q7Z553-2
	MDGA2	NM_182830.4		c.-209T>C		5_prime_UTR	Exon 4 of 17	NP_878250.2	Q7Z553-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDGA2	ENST00000399232.8	TSL:1 MANE Select	c.686T>C	p.Val229Ala	missense	Exon 4 of 17	ENSP00000382178.4	Q7Z553-3
	MDGA2	ENST00000357362.7	TSL:5	c.-209T>C		5_prime_UTR_premature_start_codon_gain	Exon 4 of 17	ENSP00000349925.3	Q7Z553-2
	MDGA2	ENST00000357362.7	TSL:5	c.-209T>C		5_prime_UTR	Exon 4 of 17	ENSP00000349925.3	Q7Z553-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.23
Eigen_PC	Benign	0.048
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		5.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.15
Sift	Benign	0.20	T
Polyphen		0.0010	B
MutPred		0.54		Gain of catalytic residue at P165 (P = 5e-04)
MVP		0.043
ClinPred		0.55	D
GERP RS		5.7
Varity_R		0.090
gMVP		0.37
Mutation Taster		=279/21	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

hg19: chr14-47613387;