7-78501664-G-C

Position:

• chr7-78501664-G-C

Variant summary

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

The ENST00000354212.9(MAGI2):​c.878C>G​(p.Thr293Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T293I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAGI2 ENST00000354212.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.32

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098353595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.878C>G	p.Thr293Ser	missense_variant	5/22	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.878C>G	p.Thr293Ser	missense_variant	5/22	1	NM_012301.4	ENSP00000346151	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	18
DANN	Benign	0.68
DEOGEN2	Benign	0.060	T;T;.;.;.;.;T;.;.;T;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.60	T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.098	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	.;L;L;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.35	.;N;N;.;.;.;.;N;.;.;.
REVEL	Benign	0.070
Sift	Benign	0.74	.;T;T;.;.;.;.;T;.;.;.
Sift4G	Benign	0.53	T;T;T;T;T;.;T;T;T;T;.
Polyphen		0.0010, 0.0020	.;B;B;.;.;.;.;.;.;.;.
Vest4		0.18, 0.18, 0.18, 0.18, 0.16, 0.23, 0.17
MutPred		0.23		.;Loss of methylation at K291 (P = 0.1068);Loss of methylation at K291 (P = 0.1068);.;.;Loss of methylation at K291 (P = 0.1068);.;Loss of methylation at K291 (P = 0.1068);.;.;.;
MVP		0.16
MPC		0.18
ClinPred		0.23	T
GERP RS		5.0
Varity_R		0.051
gMVP		0.19

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: rs587780389; hg19: chr7-78130981;