dbSNP rs2294067: MYOM2:c.2440+67C>G (chr8-2099050-C-G) – 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.2440+67C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,503,586 control chromosomes in the GnomAD database, including 134,489 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 0.38 ( 11593 hom., cov: 33)

Exomes 𝑓: 0.42 ( 122896 hom. )

Consequence

MYOM2
NM_003970.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0660

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=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 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.2440+67C>G		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.2440+67C>G	intron	N/A	ENSP00000262113.4	P54296
MYOM2	ENST00000887732.1		c.2533+67C>G	intron	N/A	ENSP00000557791.1
MYOM2	ENST00000887733.1		c.2521+67C>G	intron	N/A	ENSP00000557792.1

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

57052

AN:

152048

Hom.:

11580

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.534

Gnomad EAS

AF:

0.600

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.396

GnomAD4 exome

AF:

0.422

AC:

569708

AN:

1351420

Hom.:

122896

AF XY:

0.424

AC XY:

280263

AN XY:

660554

show subpopulations

African (AFR)

AF:

0.222

AC:

6859

AN:

30908

American (AMR)

AF:

0.273

AC:

8634

AN:

31646

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

11520

AN:

21678

East Asian (EAS)

AF:

0.583

AC:

21279

AN:

36470

South Asian (SAS)

AF:

0.482

AC:

35138

AN:

72906

European-Finnish (FIN)

AF:

0.426

AC:

20112

AN:

47188

Middle Eastern (MID)

AF:

0.498

AC:

1903

AN:

3824

European-Non Finnish (NFE)

AF:

0.419

AC:

440464

AN:

1051248

Other (OTH)

AF:

0.428

AC:

23799

AN:

55552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

16565

33130

49695

66260

82825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14010

28020

42030

56040

70050

<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:

0.375

AC:

57089

AN:

152166

Hom.:

11593

Cov.:

AF XY:

0.379

AC XY:

28171

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.230

AC:

9580

AN:

41564

American (AMR)

AF:

0.332

AC:

5083

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.534

AC:

1849

AN:

3464

East Asian (EAS)

AF:

0.600

AC:

3089

AN:

5152

South Asian (SAS)

AF:

0.495

AC:

2385

AN:

4818

European-Finnish (FIN)

AF:

0.432

AC:

4573

AN:

10578

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.428

AC:

29100

AN:

67982

Other (OTH)

AF:

0.403

AC:

852

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1732

3464

5195

6927

8659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.393

Hom.:

1547

Bravo

AF:

0.360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

4.3

(source)

PhyloP100

0.066

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over