dbSNP rs2280902: MYOM2:c.3695-43G>A (chr8-2129084-G-A) – 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.3695-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,413,670 control chromosomes in the GnomAD database, including 137,302 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 0.40 ( 12372 hom., cov: 32)

Exomes 𝑓: 0.44 ( 124930 hom. )

Consequence

MYOM2
NM_003970.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.780

Publications

23 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:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

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.3695-43G>A		intron	N/A	NP_003961.3	P54296

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYOM2	ENST00000262113.9	TSL:1 MANE Select	c.3695-43G>A	intron	N/A	ENSP00000262113.4	P54296
MYOM2	ENST00000887732.1		c.3788-43G>A	intron	N/A	ENSP00000557791.1
MYOM2	ENST00000887733.1		c.3776-43G>A	intron	N/A	ENSP00000557792.1

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60548

AN:

151902

Hom.:

12375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.504

Gnomad AMR

AF:

0.390

Gnomad ASJ

AF:

0.503

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.313

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.389

GnomAD4 exome

AF:

0.441

AC:

556792

AN:

1261650

Hom.:

124930

Cov.:

AF XY:

0.438

AC XY:

276237

AN XY:

630732

show subpopulations

African (AFR)

AF:

0.305

AC:

9101

AN:

29828

American (AMR)

AF:

0.424

AC:

18611

AN:

43924

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

12650

AN:

24406

East Asian (EAS)

AF:

0.300

AC:

11416

AN:

38040

South Asian (SAS)

AF:

0.321

AC:

26145

AN:

81446

European-Finnish (FIN)

AF:

0.409

AC:

21207

AN:

51792

Middle Eastern (MID)

AF:

0.398

AC:

2104

AN:

5286

European-Non Finnish (NFE)

AF:

0.463

AC:

432365

AN:

933898

Other (OTH)

AF:

0.437

AC:

23193

AN:

53030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

14922

29843

44765

59686

74608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12432

24864

37296

49728

62160

<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:

0.398

AC:

60561

AN:

152020

Hom.:

12372

Cov.:

AF XY:

0.394

AC XY:

29283

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.310

AC:

12833

AN:

41448

American (AMR)

AF:

0.390

AC:

5953

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.503

AC:

1744

AN:

3470

East Asian (EAS)

AF:

0.313

AC:

1618

AN:

5166

South Asian (SAS)

AF:

0.313

AC:

1507

AN:

4820

European-Finnish (FIN)

AF:

0.396

AC:

4179

AN:

10564

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.461

AC:

31336

AN:

67956

Other (OTH)

AF:

0.386

AC:

816

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1856

3712

5567

7423

9279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.427

Hom.:

18265

Bravo

AF:

0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.1

(source)

PhyloP100

-0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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