Genetic Variant MYOM2:c.4081-104C>T (chr8-2144560-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003970.4(MYOM2):c.4081-104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,141,538 control chromosomes in the GnomAD database, including 26,636 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2761 hom., cov: 33)

Exomes 𝑓: 0.21 ( 23875 hom. )

Consequence

MYOM2
NM_003970.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.142

Publications

5 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM2	NM_003970.4 link	c.4081-104C>T		intron_variant	Intron 36 of 36	ENST00000262113.9	NP_003961.3	P54296

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOM2	ENST00000262113.9 link	c.4081-104C>T		intron_variant	Intron 36 of 36	1	NM_003970.4	ENSP00000262113.4		P54296

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26474

AN:

152032

Hom.:

2764

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0584

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.223

GnomAD4 exome

AF:

0.215

AC:

212345

AN:

989388

Hom.:

23875

AF XY:

0.214

AC XY:

109299

AN XY:

509952

show subpopulations

African (AFR)

AF:

0.0552

AC:

1240

AN:

22444

American (AMR)

AF:

0.129

AC:

3982

AN:

30934

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

4538

AN:

21466

East Asian (EAS)

AF:

0.199

AC:

7455

AN:

37458

South Asian (SAS)

AF:

0.198

AC:

14157

AN:

71404

European-Finnish (FIN)

AF:

0.233

AC:

11880

AN:

50950

Middle Eastern (MID)

AF:

0.241

AC:

1160

AN:

4822

European-Non Finnish (NFE)

AF:

0.225

AC:

158463

AN:

705390

Other (OTH)

AF:

0.213

AC:

9470

AN:

44520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

8961

17921

26882

35842

44803

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4282

8564

12846

17128

21410

<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:

0.174

AC:

26468

AN:

152150

Hom.:

2761

Cov.:

AF XY:

0.176

AC XY:

13122

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0583

AC:

2422

AN:

41534

American (AMR)

AF:

0.186

AC:

2837

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

755

AN:

3472

East Asian (EAS)

AF:

0.182

AC:

938

AN:

5150

South Asian (SAS)

AF:

0.191

AC:

919

AN:

4822

European-Finnish (FIN)

AF:

0.249

AC:

2636

AN:

10592

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.225

AC:

15273

AN:

67972

Other (OTH)

AF:

0.221

AC:

467

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1098

2195

3293

4390

5488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

294

588

882

1176

1470

<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:

0.190

Hom.:

1701

Bravo

AF:

0.167

Asia WGS

AF:

0.181

AC:

628

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.51

(source)

DANN

Benign

0.62

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over