rs11525066

Positions:

• chr7-78546660-G-A
• chr7-78546660-G-T

Variant summary

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

The NM_012301.4(MAGI2):​c.539-25015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 139,588 control chromosomes in the GnomAD database, including 386 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 0.067 (386 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.539-25015C>T		intron_variant		ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.539-25015C>T		intron_variant		1	NM_012301.4	ENSP00000346151	P4

Frequencies

GnomAD3 genomes AF: 0.0675 AC: 9420 AN: 139480 Hom.: 385 Cov.: 32

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.0135

Gnomad AMR AF: 0.0706

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.0321

Gnomad SAS AF: 0.0717

Gnomad FIN AF: 0.0745

Gnomad MID AF: 0.0588

Gnomad NFE AF: 0.0949

Gnomad OTH AF: 0.0807

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

GnomAD4 genome AF: 0.0675 AC: 9421 AN: 139588 Hom.: 386 Cov.: 32 AF XY: 0.0662 AC XY: 4465 AN XY: 67464

Gnomad4 AFR AF: 0.0189

Gnomad4 AMR AF: 0.0706

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.0320

Gnomad4 SAS AF: 0.0726

Gnomad4 FIN AF: 0.0745

Gnomad4 NFE AF: 0.0949

Gnomad4 OTH AF: 0.0796

Alfa AF: 0.0824 Hom.: 777

Bravo AF: 0.0608

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.60

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: rs11525066; hg19: chr7-78175977;