rs6953482

Variant names:

• chr7-78737912-A-G
• rs6953482
• NM_012301.4:c.419-110673T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-78737912-A-G
• chr7-78737912-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012301.4(MAGI2):​c.419-110673T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,844 control chromosomes in the GnomAD database, including 15,262 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 0.44 (15262 hom., cov: 31)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• nephrotic syndrome 15

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• epilepsy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.419-110673T>C		intron_variant	Intron 2 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.419-110673T>C		intron_variant	Intron 2 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67282 AN: 151726 Hom.: 15257 Cov.: 31

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.443 AC: 67316 AN: 151844 Hom.: 15262 Cov.: 31 AF XY: 0.434 AC XY: 32205 AN XY: 74208

African (AFR) AF: 0.467 AC: 19320 AN: 41412

American (AMR) AF: 0.400 AC: 6103 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1576 AN: 3462

East Asian (EAS) AF: 0.294 AC: 1517 AN: 5164

South Asian (SAS) AF: 0.287 AC: 1382 AN: 4812

European-Finnish (FIN) AF: 0.381 AC: 4010 AN: 10536

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32007 AN: 67902

Other (OTH) AF: 0.463 AC: 977 AN: 2110

Alfa AF: 0.452 Hom.: 1882

Bravo AF: 0.451

Asia WGS AF: 0.289 AC: 1005 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.66
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6953482; hg19: chr7-78367228;