NM_012301.4:c.418+66257C>T

Variant names:

• chr7-78940833-G-A
• rs17151725
• NM_012301.4:c.418+66257C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012301.4(MAGI2):​c.418+66257C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,022 control chromosomes in the GnomAD database, including 11,488 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (11486 hom., cov: 32)
  • Exomes 𝑓: 0.39 (2 hom.)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 3 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-AS1 (HGNC:40860): (MAGI2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.418+66257C>T		intron_variant	Intron 2 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.418+66257C>T		intron_variant	Intron 2 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53456 AN: 151886 Hom.: 11491 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.389 AC: 7 AN: 18 Hom.: 2 Cov.: 0 AF XY: 0.286 AC XY: 4 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.417 AC: 5 AN: 12

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.352 AC: 53446 AN: 152004 Hom.: 11486 Cov.: 32 AF XY: 0.352 AC XY: 26160 AN XY: 74272

African (AFR) AF: 0.100 AC: 4155 AN: 41508

American (AMR) AF: 0.341 AC: 5213 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1832 AN: 3468

East Asian (EAS) AF: 0.489 AC: 2507 AN: 5126

South Asian (SAS) AF: 0.304 AC: 1464 AN: 4822

European-Finnish (FIN) AF: 0.519 AC: 5471 AN: 10544

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31383 AN: 67950

Other (OTH) AF: 0.392 AC: 826 AN: 2106

Alfa AF: 0.384 Hom.: 2141

Bravo AF: 0.334

Asia WGS AF: 0.363 AC: 1262 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.44
DANN	Benign	0.66
PhyloP100		-1.8
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: rs17151725; hg19: chr7-78570149;