Genetic Variant MIGA2:p.Ser203Ser (chr9-129049897-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001329990.2(MIGA2):c.609C>T(p.Ser203Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,613,810 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 71 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 71 hom. )

Consequence

MIGA2
NM_001329990.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.23

Variant links:

Genes affected

MIGA2 (HGNC:23621): (mitoguardin 2) Enables protein heterodimerization activity and protein homodimerization activity. Involved in mitochondrial fusion. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MIGA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 9-129049897-C-T is Benign according to our data. Variant chr9-129049897-C-T is described in ClinVar as [Benign]. Clinvar id is 774439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIGA2	NM_001329990.2 link	c.609C>T	p.Ser203Ser	synonymous_variant	Exon 6 of 16	ENST00000684074.1	NP_001316919.1	Q7L4E1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MIGA2	ENST00000684074.1 link	c.609C>T	p.Ser203Ser	synonymous_variant	Exon 6 of 16		NM_001329990.2	ENSP00000506871.1	Q7L4E1-1
MIGA2	ENST00000358369.8 link	c.609C>T	p.Ser203Ser	synonymous_variant	Exon 6 of 16	1		ENSP00000351138.4	Q7L4E1-1
MIGA2	ENST00000439290.5 link	n.609C>T		non_coding_transcript_exon_variant	Exon 6 of 17	2		ENSP00000391603.1	Q7L4E1-2
MIGA2	ENST00000445183.5 link	n.609C>T		non_coding_transcript_exon_variant	Exon 6 of 14	2		ENSP00000396618.1	Q7L4E1-3

Frequencies

GnomAD3 genomes

AF:

0.0167

AC:

2535

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0525

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.00592

AC:

1485

AN:

250854

Hom.:

AF XY:

0.00470

AC XY:

638

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.0568

Gnomad AMR exome

AF:

0.00672

Gnomad ASJ exome

AF:

0.0115

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00144

Gnomad OTH exome

AF:

0.00605

GnomAD4 exome

AF:

0.00295

AC:

4312

AN:

1461526

Hom.:

Cov.:

AF XY:

0.00284

AC XY:

2066

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.0586

Gnomad4 AMR exome

AF:

0.00694

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.00699

GnomAD4 genome

AF:

0.0168

AC:

2553

AN:

152284

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1225

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0527

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.00881

Hom.:

Bravo

AF:

0.0192

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00180

EpiControl

AF:

0.00148

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 06, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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

-0.69

CADD

Benign

1.1

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over