rs1990577

Variant names:

• chr7-78489882-A-C
• rs1990577
• NM_012301.4:c.966-42T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-78489882-A-C
• chr7-78489882-A-G
• chr7-78489882-A-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_012301.4(MAGI2):​c.966-42T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,432,782 control chromosomes in the GnomAD database, including 223,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (24049 hom., cov: 30)
  • Exomes 𝑓: 0.55 (199226 hom.)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.03
• Publications: 6 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 7-78489882-A-C is Benign according to our data. Variant chr7-78489882-A-C is described in ClinVar as Benign. ClinVar VariationId is 1237001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012301.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	NM_012301.4	MANE Select	c.966-42T>G		intron	N/A	NP_036433.2
	MAGI2	NM_001301128.2		c.966-42T>G		intron	N/A	NP_001288057.1	Q86UL8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	ENST00000354212.9	TSL:1 MANE Select	c.966-42T>G		intron	N/A	ENSP00000346151.4	Q86UL8-1
	MAGI2	ENST00000419488.5	TSL:1	c.966-42T>G		intron	N/A	ENSP00000405766.1	Q86UL8-2
	MAGI2	ENST00000519748.5	TSL:1	c.-208-42T>G		intron	N/A	ENSP00000486774.1	A0A0D9SFP3

Frequencies

GnomAD3 genomes AF: 0.571 AC: 84585 AN: 148040 Hom.: 24030 Cov.: 30

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.576

GnomAD2 exomes AF: 0.606 AC: 133969 AN: 221162 AF XY: 0.601

Gnomad AFR exome AF: 0.539

Gnomad AMR exome AF: 0.751

Gnomad ASJ exome AF: 0.565

Gnomad EAS exome AF: 0.774

Gnomad FIN exome AF: 0.582

Gnomad NFE exome AF: 0.546

Gnomad OTH exome AF: 0.584

GnomAD4 exome AF: 0.553 AC: 710326 AN: 1284628 Hom.: 199226 Cov.: 17 AF XY: 0.554 AC XY: 358118 AN XY: 646316

African (AFR) AF: 0.526 AC: 14873 AN: 28286

American (AMR) AF: 0.725 AC: 26575 AN: 36668

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 12868 AN: 23558

East Asian (EAS) AF: 0.761 AC: 29526 AN: 38794

South Asian (SAS) AF: 0.647 AC: 50121 AN: 77438

European-Finnish (FIN) AF: 0.576 AC: 30200 AN: 52414

Middle Eastern (MID) AF: 0.486 AC: 2565 AN: 5282

European-Non Finnish (NFE) AF: 0.531 AC: 513723 AN: 968214

Other (OTH) AF: 0.554 AC: 29875 AN: 53974

GnomAD4 genome AF: 0.571 AC: 84643 AN: 148154 Hom.: 24049 Cov.: 30 AF XY: 0.577 AC XY: 41681 AN XY: 72180

African (AFR) AF: 0.548 AC: 21864 AN: 39882

American (AMR) AF: 0.655 AC: 9686 AN: 14788

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1842 AN: 3434

East Asian (EAS) AF: 0.775 AC: 3954 AN: 5102

South Asian (SAS) AF: 0.668 AC: 3134 AN: 4690

European-Finnish (FIN) AF: 0.594 AC: 6003 AN: 10098

Middle Eastern (MID) AF: 0.500 AC: 141 AN: 282

European-Non Finnish (NFE) AF: 0.544 AC: 36382 AN: 66926

Other (OTH) AF: 0.572 AC: 1177 AN: 2058

Alfa AF: 0.532 Hom.: 13201

Bravo AF: 0.561

Asia WGS AF: 0.682 AC: 2371 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		2.0
PromoterAI		-0.0044	Neutral
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: rs1990577; hg19: chr7-78119199;