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:

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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=-0.92).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM2	NM_003970.4 link	c.3695-43G>A		intron_variant	Intron 31 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.3695-43G>A		intron_variant	Intron 31 of 36	1	NM_003970.4	ENSP00000262113.4		P54296

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 v4.3

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

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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