chr7-79453287-T-A

Variant names:

• chr7-79453287-T-A
• rs1849422277
• NM_012301.4:c.34A>T

Variant summary

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

The NM_012301.4(MAGI2):​c.34A>T​(p.Thr12Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAGI2 NM_012301.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83

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]

MAGI2-AS3 (HGNC:40862): (MAGI2 antisense RNA 3)

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=0.2391578).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.34A>T	p.Thr12Ser	missense_variant	Exon 1 of 22	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.34A>T	p.Thr12Ser	missense_variant	Exon 1 of 22	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nephrotic syndrome 15 Uncertain:1

Feb 29, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.19	T;.;.;.
Eigen	Benign	0.045
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L;L;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.0	N;N;.;N
REVEL	Benign	0.14
Sift	Benign	0.52	T;T;.;T
Sift4G	Benign	0.60	T;T;.;T
Polyphen		0.087	B;P;.;.
Vest4		0.56
MutPred		0.24		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.45
MPC		1.8
ClinPred		0.83	D
GERP RS		5.2
Varity_R		0.16
gMVP		0.43

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: rs1849422277; hg19: chr7-79082603;