rs373777210

Variant names:

• chr7-78256252-C-A
• NM_012301.4:c.1738G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-78256252-C-A
• chr7-78256252-C-G
• chr7-78256252-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012301.4(MAGI2):​c.1738G>T​(p.Gly580Cys) 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 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MAGI2 NM_012301.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.33

Genes affected

MAGI2 (HGNC:18957): (membrane associated guanylate kinase, WW and PDZ domain containing 2) The protein encoded by this gene interacts with atrophin-1. Atrophin-1 contains a polyglutamine repeat, expansion of which is responsible for dentatorubral and pallidoluysian atrophy. This encoded protein is characterized by two WW domains, a guanylate kinase-like domain, and multiple PDZ domains. It has structural similarity to the membrane-associated guanylate kinase homologue (MAGUK) family. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3479032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.1738G>T	p.Gly580Cys	missense_variant	Exon 10 of 22	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.1738G>T	p.Gly580Cys	missense_variant	Exon 10 of 22	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461732 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

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	0.10
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;D;.;.;.;.;T;.;.;.;T;.;.;T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.35	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	.;M;M;.;.;.;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.9	.;D;D;.;.;.;.;D;.;.;.;.;.;.;.
REVEL	Benign	0.15
Sift	Uncertain	0.0020	.;D;D;.;.;.;.;D;.;.;.;.;.;.;.
Sift4G	Uncertain	0.0030	D;D;D;D;D;.;D;D;.;D;.;.;D;D;.
Polyphen		1.0, 1.0, 0.97	.;D;D;.;.;.;.;D;.;.;.;.;.;.;.
Vest4		0.49, 0.39, 0.42, 0.40, 0.40, 0.46, 0.32, 0.28
MutPred		0.32		.;Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);.;.;Loss of relative solvent accessibility (P = 0.0676);.;Loss of relative solvent accessibility (P = 0.0676);.;.;.;.;.;.;.;
MVP		0.24
MPC		0.75
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.37
gMVP		0.46

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: chr7-77885569;