Genetic Variant MIGA2:p.Arg243Cys (chr9-129059205-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001329990.2(MIGA2):c.727C>T(p.Arg243Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00151 in 1,611,792 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 3 hom. )

Consequence

MIGA2
NM_001329990.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21145916).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329990.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIGA2	NM_001329990.2	MANE Select	c.727C>T	p.Arg243Cys	missense	Exon 7 of 16	NP_001316919.1	Q7L4E1-1
MIGA2	NM_032809.4		c.919C>T	p.Arg307Cys	missense	Exon 7 of 16	NP_116198.3
MIGA2	NR_138421.2		n.1047C>T		non_coding_transcript_exon	Exon 8 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIGA2	ENST00000684074.1	MANE Select	c.727C>T	p.Arg243Cys	missense	Exon 7 of 16	ENSP00000506871.1	Q7L4E1-1
MIGA2	ENST00000358369.8	TSL:1	c.727C>T	p.Arg243Cys	missense	Exon 7 of 16	ENSP00000351138.4	Q7L4E1-1
MIGA2	ENST00000942817.1		c.727C>T	p.Arg243Cys	missense	Exon 7 of 16	ENSP00000612876.1

Frequencies

GnomAD3 genomes

AF:

0.00113

AC:

172

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00218

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000960

AC:

234

AN:

243804

AF XY:

0.000893

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.000323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000581

Gnomad NFE exome

AF:

0.00185

Gnomad OTH exome

AF:

0.000503

GnomAD4 exome

AF:

0.00155

AC:

2265

AN:

1459590

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

1066

AN XY:

725864

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33436

American (AMR)

AF:

0.000225

AC:

AN:

44426

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85796

European-Finnish (FIN)

AF:

0.000469

AC:

AN:

53250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00194

AC:

2159

AN:

1110920

Other (OTH)

AF:

0.000879

AC:

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

113

226

338

451

564

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00113

AC:

172

AN:

152202

Hom.:

Cov.:

AF XY:

0.000982

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.000314

AC:

AN:

41444

American (AMR)

AF:

0.000131

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00218

AC:

148

AN:

68032

Other (OTH)

AF:

0.000957

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00177

Hom.:

Bravo

AF:

0.00109

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000916

AC:

111

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.68

PhyloP100

4.5

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.83

MVP

0.70

MPC

1.2

ClinPred

0.12

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.63

Mutation Taster

=70/30

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over