7-78019494-TGCC-TGCCGCC

Variant names:

• chr7-78019494-T-TGCC
• rs797045686
• NM_012301.4:c.4186_4188dupGGC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PM4_Supporting

The NM_012301.4(MAGI2):​c.4186_4188dupGGC​(p.Gly1396dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000531 in 979,496 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000048 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000054 (0 hom.)
• Consequence: MAGI2 NM_012301.4 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.249
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_012301.4. Strenght limited to Supporting due to length of the change: 1aa.

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.4186_4188dupGGC	p.Gly1396dup	conservative_inframe_insertion	Exon 22 of 22	NP_036433.2
	MAGI2	NM_001301128.2		c.4144_4146dupGGC	p.Gly1382dup	conservative_inframe_insertion	Exon 21 of 21	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.4186_4188dupGGC	p.Gly1396dup	conservative_inframe_insertion	Exon 22 of 22	ENSP00000346151.4	Q86UL8-1
	MAGI2	ENST00000419488.5	TSL:1	c.4144_4146dupGGC	p.Gly1382dup	conservative_inframe_insertion	Exon 21 of 21	ENSP00000405766.1	Q86UL8-2
	MAGI2	ENST00000522391.3	TSL:5	c.*423_*425dupGGC		3_prime_UTR	Exon 23 of 23	ENSP00000428389.1	E7EWI0

Frequencies

GnomAD3 genomes AF: 0.0000483 AC: 7 AN: 144846 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000612

Gnomad OTH AF: 0.000501

GnomAD4 exome AF: 0.0000539 AC: 45 AN: 834650 Hom.: 0 Cov.: 30 AF XY: 0.0000441 AC XY: 17 AN XY: 385730

African (AFR) AF: 0.00 AC: 0 AN: 15792

American (AMR) AF: 0.00 AC: 0 AN: 1002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5164

East Asian (EAS) AF: 0.00 AC: 0 AN: 3688

South Asian (SAS) AF: 0.000117 AC: 2 AN: 17132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1620

European-Non Finnish (NFE) AF: 0.0000538 AC: 41 AN: 762634

Other (OTH) AF: 0.0000732 AC: 2 AN: 27330

GnomAD4 genome AF: 0.0000483 AC: 7 AN: 144846 Hom.: 0 Cov.: 30 AF XY: 0.0000426 AC XY: 3 AN XY: 70400

African (AFR) AF: 0.0000494 AC: 2 AN: 40506

American (AMR) AF: 0.00 AC: 0 AN: 14662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3382

East Asian (EAS) AF: 0.00 AC: 0 AN: 4930

South Asian (SAS) AF: 0.00 AC: 0 AN: 4706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000612 AC: 4 AN: 65326

Other (OTH) AF: 0.000501 AC: 1 AN: 1998

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25
Mutation Taster		=87/13	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs797045686; hg19: chr7-77648811;