NM_012301.4:c.276C>G

Variant names:

• chr7-79453045-G-C
• rs146012909
• NM_012301.4:c.276C>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_012301.4(MAGI2):​c.276C>G​(p.Pro92Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,602,380 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (2 hom., cov: 32)
  • Exomes 𝑓: 0.010 (127 hom.)
• Consequence: MAGI2 NM_012301.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.03
• Publications: 2 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-AS3 (HGNC:40862): (MAGI2 antisense RNA 3)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 7-79453045-G-C is Benign according to our data. Variant chr7-79453045-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.03 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

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.276C>G	p.Pro92Pro	synonymous	Exon 1 of 22	NP_036433.2
	MAGI2	NM_001301128.2		c.276C>G	p.Pro92Pro	synonymous	Exon 1 of 21	NP_001288057.1	Q86UL8-2
	MAGI2-AS3	NR_038345.1		n.89G>C		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	ENST00000354212.9	TSL:1 MANE Select	c.276C>G	p.Pro92Pro	synonymous	Exon 1 of 22	ENSP00000346151.4	Q86UL8-1
	MAGI2	ENST00000419488.5	TSL:1	c.276C>G	p.Pro92Pro	synonymous	Exon 1 of 21	ENSP00000405766.1	Q86UL8-2
	MAGI2	ENST00000522391.3	TSL:5	c.276C>G	p.Pro92Pro	synonymous	Exon 1 of 23	ENSP00000428389.1	E7EWI0

Frequencies

GnomAD3 genomes AF: 0.00597 AC: 909 AN: 152196 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00676 AC: 1635 AN: 242030 AF XY: 0.00725

Gnomad AFR exome AF: 0.00217

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00154

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.00664

GnomAD4 exome AF: 0.0105 AC: 15165 AN: 1450066 Hom.: 127 Cov.: 31 AF XY: 0.0103 AC XY: 7424 AN XY: 720146

African (AFR) AF: 0.00126 AC: 42 AN: 33354

American (AMR) AF: 0.00143 AC: 63 AN: 44172

Ashkenazi Jewish (ASJ) AF: 0.00147 AC: 37 AN: 25198

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39580

South Asian (SAS) AF: 0.0112 AC: 952 AN: 84642

European-Finnish (FIN) AF: 0.00208 AC: 108 AN: 51824

Middle Eastern (MID) AF: 0.00246 AC: 14 AN: 5682

European-Non Finnish (NFE) AF: 0.0123 AC: 13551 AN: 1105668

Other (OTH) AF: 0.00661 AC: 396 AN: 59946

GnomAD4 genome AF: 0.00596 AC: 908 AN: 152314 Hom.: 2 Cov.: 32 AF XY: 0.00549 AC XY: 409 AN XY: 74460

African (AFR) AF: 0.00166 AC: 69 AN: 41576

American (AMR) AF: 0.00196 AC: 30 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00746 AC: 36 AN: 4828

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 726 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00708 Hom.: 2

Bravo AF: 0.00567

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	MAGI2-related disorder (1)
-	-	1	Nephrotic syndrome 15 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		1.0
PromoterAI		-0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs146012909; hg19: chr7-79082361;