rs6951193

Positions:

• chr7-78478986-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012301.4(MAGI2):​c.1045+10775T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,764 control chromosomes in the GnomAD database, including 7,279 homozygotes. 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: 𝑓 0.30 (7279 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.1045+10775T>C		intron_variant		ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.1045+10775T>C		intron_variant		1	NM_012301.4	ENSP00000346151	P4

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46045 AN: 151646 Hom.: 7279 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.326

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.304 AC: 46075 AN: 151764 Hom.: 7279 Cov.: 32 AF XY: 0.309 AC XY: 22903 AN XY: 74168

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.323

Alfa AF: 0.300 Hom.: 9277

Bravo AF: 0.300

Asia WGS AF: 0.445 AC: 1546 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6951193; hg19: chr7-78108303;