chr7-78019249-C-G

Variant names:

• chr7-78019249-C-G
• rs188597942
• NM_012301.4:c.*66G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_012301.4(MAGI2):​c.*66G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00798 in 1,546,494 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (74 hom.)
• Consequence: MAGI2 NM_012301.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.34
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.068).
• BP6: Variant 7-78019249-C-G is Benign according to our data. Variant chr7-78019249-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1343875.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.*66G>C		3_prime_UTR_variant	Exon 22 of 22	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.*66G>C		3_prime_UTR_variant	Exon 22 of 22	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.00723 AC: 1100 AN: 152108 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00887

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00635 AC: 1113 AN: 175360 AF XY: 0.00609

Gnomad AFR exome AF: 0.00134

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.000117

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0343

Gnomad NFE exome AF: 0.00979

Gnomad OTH exome AF: 0.00769

GnomAD4 exome AF: 0.00807 AC: 11246 AN: 1394268 Hom.: 74 Cov.: 24 AF XY: 0.00787 AC XY: 5446 AN XY: 692404

African (AFR) AF: 0.00144 AC: 46 AN: 31950

American (AMR) AF: 0.00151 AC: 61 AN: 40410

Ashkenazi Jewish (ASJ) AF: 0.000238 AC: 6 AN: 25240

East Asian (EAS) AF: 0.0000535 AC: 2 AN: 37410

South Asian (SAS) AF: 0.00 AC: 0 AN: 80674

European-Finnish (FIN) AF: 0.0313 AC: 1114 AN: 35570

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5692

European-Non Finnish (NFE) AF: 0.00896 AC: 9667 AN: 1078916

Other (OTH) AF: 0.00598 AC: 349 AN: 58406

GnomAD4 genome AF: 0.00722 AC: 1099 AN: 152226 Hom.: 8 Cov.: 32 AF XY: 0.00805 AC XY: 599 AN XY: 74422

African (AFR) AF: 0.00149 AC: 62 AN: 41576

American (AMR) AF: 0.00222 AC: 34 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0368 AC: 390 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00885 AC: 602 AN: 67990

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00674 Hom.: 4

Bravo AF: 0.00465

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 17, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.73
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs188597942; hg19: chr7-77648566;