dbSNP rs10988183: MIGA2:p.Asp211Asp (chr9-129049921-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001329990.2(MIGA2):c.633C>T(p.Asp211Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,613,730 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00095 ( 34 hom. )

Consequence

MIGA2
NM_001329990.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.132

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: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 9-129049921-C-T is Benign according to our data. Variant chr9-129049921-C-T is described in ClinVar as [Benign]. Clinvar id is 773784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.132 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00175 (267/152334) while in subpopulation EAS AF = 0.0411 (213/5178). AF 95% confidence interval is 0.0366. There are 8 homozygotes in GnomAd4. There are 140 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIGA2	NM_001329990.2 link	c.633C>T	p.Asp211Asp	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.633C>T	p.Asp211Asp	synonymous_variant	Exon 6 of 16		NM_001329990.2	ENSP00000506871.1	Q7L4E1-1
MIGA2	ENST00000358369.8 link	c.633C>T	p.Asp211Asp	synonymous_variant	Exon 6 of 16	1		ENSP00000351138.4	Q7L4E1-1
MIGA2	ENST00000439290.5 link	n.633C>T		non_coding_transcript_exon_variant	Exon 6 of 17	2		ENSP00000391603.1	Q7L4E1-2
MIGA2	ENST00000445183.5 link	n.633C>T		non_coding_transcript_exon_variant	Exon 6 of 14	2		ENSP00000396618.1	Q7L4E1-3

Frequencies

GnomAD3 genomes

AF:

0.00175

AC:

267

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0408

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00317

AC:

795

AN:

250614

AF XY:

0.00299

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0401

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.000949

AC:

1387

AN:

1461396

Hom.:

Cov.:

AF XY:

0.000915

AC XY:

665

AN XY:

727014

show subpopulations

African (AFR)

AF:

0.000627

AC:

AN:

33468

American (AMR)

AF:

0.000246

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.0253

AC:

1003

AN:

39700

South Asian (SAS)

AF:

0.000684

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53060

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000333

AC:

AN:

1111952

Other (OTH)

AF:

0.00422

AC:

255

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

161

241

322

402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00175

AC:

267

AN:

152334

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000794

AC:

AN:

41586

American (AMR)

AF:

0.000196

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0411

AC:

213

AN:

5178

South Asian (SAS)

AF:

0.00187

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68038

Other (OTH)

AF:

0.00284

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000629

Hom.:

Bravo

AF:

0.00196

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

- -

Apr 16, 2018

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

-0.42

CADD

Benign

2.3

(source)

DANN

Benign

0.29

PhyloP100

-0.13

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

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rs10988183

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over