Genetic Variant MYOM2:p.Arg74Gln (chr8-2052271-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_003970.4(MYOM2):c.221G>A(p.Arg74Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000028 in 1,609,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MYOM2
NM_003970.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.76

Publications

2 publications found

Variant links:

Genes affected

MYOM2 (HGNC:7614): (myomesin 2) The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents of apparent molecular masses of 190 kD and 165 kD. The predicted MYOM2 protein contains 1,465 amino acids. Like MYOM1, MYOM2 has a unique N-terminal domain followed by 12 repeat domains with strong homology to either fibronectin type III or immunoglobulin C2 domains. Protein sequence comparisons suggested that the MYOM2 protein and bovine M protein are identical. [provided by RefSeq, Jul 2008]

MYOM2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.4049248).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003970.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOM2	NM_003970.4	MANE Select	c.221G>A	p.Arg74Gln	missense	Exon 3 of 37	NP_003961.3	P54296

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYOM2	ENST00000262113.9	TSL:1 MANE Select	c.221G>A	p.Arg74Gln	missense	Exon 3 of 37	ENSP00000262113.4	P54296
MYOM2	ENST00000887732.1		c.221G>A	p.Arg74Gln	missense	Exon 3 of 38	ENSP00000557791.1
MYOM2	ENST00000887733.1		c.221G>A	p.Arg74Gln	missense	Exon 3 of 38	ENSP00000557792.1

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000446

AC:

AN:

246618

AF XY:

0.00000750

show subpopulations

Gnomad AFR exome

AF:

0.000619

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1457336

Hom.:

Cov.:

AF XY:

0.00000966

AC XY:

AN XY:

724726

show subpopulations

African (AFR)

AF:

0.000390

AC:

AN:

33358

American (AMR)

AF:

0.00

AC:

AN:

44152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26048

East Asian (EAS)

AF:

0.00

AC:

AN:

39568

South Asian (SAS)

AF:

0.0000234

AC:

AN:

85380

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.000197

AC:

AN:

5074

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110172

Other (OTH)

AF:

0.0000166

AC:

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000177

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.000651

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.000165

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

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

0.17

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

0.99

Eigen

Benign

0.15

Eigen_PC

Benign

0.066

FATHMM_MKL

Uncertain

0.87

M_CAP

Benign

0.031

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.92

PhyloP100

5.8

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.88

REVEL

Benign

0.25

Sift

Benign

0.069

Sift4G

Benign

0.10

Vest4

0.66

MVP

0.47

MPC

0.011

ClinPred

0.085

GERP RS

4.7

gMVP

0.34

Mutation Taster

=94/6

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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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