rs10485936

Positions:

• chr7-79218746-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_012301.4(MAGI2):​c.302-211540T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 152,222 control chromosomes in the GnomAD database, including 100 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 0.029 (100 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.592

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=-0.84).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.029 (4414/152222) while in subpopulation AFR AF= 0.0462 (1916/41468). AF 95% confidence interval is 0.0445. There are 100 homozygotes in gnomad4. There are 2196 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 100 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI2	NM_012301.4	c.302-211540T>G		intron_variant		ENST00000354212.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI2	ENST00000354212.9	c.302-211540T>G		intron_variant		1	NM_012301.4	P4

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4420 AN: 152104 Hom.: 100 Cov.: 32

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.0459

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.0320

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

GnomAD4 genome AF: 0.0290 AC: 4414 AN: 152222 Hom.: 100 Cov.: 32 AF XY: 0.0295 AC XY: 2196 AN XY: 74448

Gnomad4 AFR AF: 0.0462

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.0396

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.0459

Gnomad4 NFE AF: 0.0189

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0258 Hom.: 21

Bravo AF: 0.0283

Asia WGS AF: 0.0330 AC: 115 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.79

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: rs10485936; hg19: chr7-78848062;