NM_012301.4:c.219C>G

Variant names:

• chr7-79453102-G-C
• rs148240352
• NM_012301.4:c.219C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_012301.4(MAGI2):​c.219C>G​(p.Pro73Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P73P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAGI2 NM_012301.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.108
• 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-AS3 (HGNC:40862): (MAGI2 antisense RNA 3)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 7-79453102-G-C is Benign according to our data. Variant chr7-79453102-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3677546.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.108 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	NM_012301.4	MANE Select	c.219C>G	p.Pro73Pro	synonymous	Exon 1 of 22	NP_036433.2
	MAGI2	NM_001301128.2		c.219C>G	p.Pro73Pro	synonymous	Exon 1 of 21	NP_001288057.1
	MAGI2-AS3	NR_038345.1		n.146G>C		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	ENST00000354212.9	TSL:1 MANE Select	c.219C>G	p.Pro73Pro	synonymous	Exon 1 of 22	ENSP00000346151.4
	MAGI2	ENST00000419488.5	TSL:1	c.219C>G	p.Pro73Pro	synonymous	Exon 1 of 21	ENSP00000405766.1
	MAGI2	ENST00000522391.3	TSL:5	c.219C>G	p.Pro73Pro	synonymous	Exon 1 of 23	ENSP00000428389.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 01, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		-0.11
PromoterAI		-0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs148240352; hg19: chr7-79082418;