7-78489792-C-T

Variant names:

• chr7-78489792-C-T
• rs3735442
• NM_012301.4:c.1014G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_012301.4(MAGI2):​c.1014G>A​(p.Lys338Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,610,112 control chromosomes in the GnomAD database, including 76,886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8564 hom., cov: 32)
  • Exomes 𝑓: 0.30 (68322 hom.)
• Consequence: MAGI2 NM_012301.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.67
• Publications: 19 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 7-78489792-C-T is Benign according to our data. Variant chr7-78489792-C-T is described in ClinVar as Benign. ClinVar VariationId is 129557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.67 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 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.1014G>A	p.Lys338Lys	synonymous	Exon 6 of 22	NP_036433.2
	MAGI2	NM_001301128.2		c.1014G>A	p.Lys338Lys	synonymous	Exon 6 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.1014G>A	p.Lys338Lys	synonymous	Exon 6 of 22	ENSP00000346151.4	Q86UL8-1
	MAGI2	ENST00000419488.5	TSL:1	c.1014G>A	p.Lys338Lys	synonymous	Exon 6 of 21	ENSP00000405766.1	Q86UL8-2
	MAGI2	ENST00000519748.5	TSL:1	c.-160G>A		5_prime_UTR	Exon 2 of 16	ENSP00000486774.1	A0A0D9SFP3

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49520 AN: 151548 Hom.: 8539 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.317

GnomAD2 exomes AF: 0.288 AC: 71929 AN: 249956 AF XY: 0.291

Gnomad AFR exome AF: 0.433

Gnomad AMR exome AF: 0.193

Gnomad ASJ exome AF: 0.308

Gnomad EAS exome AF: 0.237

Gnomad FIN exome AF: 0.284

Gnomad NFE exome AF: 0.298

Gnomad OTH exome AF: 0.304

GnomAD4 exome AF: 0.303 AC: 442211 AN: 1458446 Hom.: 68322 Cov.: 33 AF XY: 0.303 AC XY: 219956 AN XY: 725486

African (AFR) AF: 0.437 AC: 14571 AN: 33348

American (AMR) AF: 0.203 AC: 9061 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 8037 AN: 26044

East Asian (EAS) AF: 0.239 AC: 9472 AN: 39650

South Asian (SAS) AF: 0.301 AC: 25863 AN: 85836

European-Finnish (FIN) AF: 0.289 AC: 15410 AN: 53342

Middle Eastern (MID) AF: 0.385 AC: 2214 AN: 5754

European-Non Finnish (NFE) AF: 0.305 AC: 338642 AN: 1109682

Other (OTH) AF: 0.314 AC: 18941 AN: 60240

GnomAD4 genome AF: 0.327 AC: 49586 AN: 151666 Hom.: 8564 Cov.: 32 AF XY: 0.324 AC XY: 23974 AN XY: 74082

African (AFR) AF: 0.427 AC: 17661 AN: 41366

American (AMR) AF: 0.257 AC: 3897 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3466

East Asian (EAS) AF: 0.227 AC: 1163 AN: 5128

South Asian (SAS) AF: 0.294 AC: 1418 AN: 4816

European-Finnish (FIN) AF: 0.283 AC: 2973 AN: 10508

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20492 AN: 67878

Other (OTH) AF: 0.323 AC: 682 AN: 2112

Alfa AF: 0.310 Hom.: 12366

Bravo AF: 0.329

Asia WGS AF: 0.290 AC: 1009 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		1.7
PromoterAI		-0.045	Neutral
Mutation Taster		=96/4	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: rs3735442; hg19: chr7-78119109; COSMIC: COSV62640934; COSMIC: COSV62640934;