chr14-46957434-C-T

Variant names:

• chr14-46957434-C-T
• NM_001113498.3:c.2029G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001113498.3(MDGA2):​c.2029G>A​(p.Val677Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MDGA2 NM_001113498.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16238597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDGA2	NM_001113498.3	c.2029G>A	p.Val677Ile	missense_variant	Exon 9 of 17	ENST00000399232.8	NP_001106970.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDGA2	ENST00000399232.8	c.2029G>A	p.Val677Ile	missense_variant	Exon 9 of 17	1	NM_001113498.3	ENSP00000382178.4
MDGA2	ENST00000357362.7	c.1135G>A	p.Val379Ile	missense_variant	Exon 9 of 17	5		ENSP00000349925.3
MDGA2	ENST00000557238.5	n.*407G>A		non_coding_transcript_exon_variant	Exon 9 of 14	5		ENSP00000452593.1
MDGA2	ENST00000557238.5	n.*407G>A		3_prime_UTR_variant	Exon 9 of 14	5		ENSP00000452593.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461828 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	.;.;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.089
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;.;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.50	N;N;.
REVEL	Benign	0.053
Sift	Benign	0.19	T;T;.
Sift4G	Benign	0.58	.;T;.
Polyphen		0.0	.;.;B
Vest4		0.054
MutPred		0.35		.;.;Gain of catalytic residue at S612 (P = 0.001);
MVP		0.35
MPC		0.14
ClinPred		0.11	T
GERP RS		4.3
Varity_R		0.053
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-47426637;