rs2294067

chr8-2099050-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOM2	NM_003970.4	c.2440+67C>G		intron_variant		ENST00000262113.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOM2	ENST00000262113.9	c.2440+67C>G		intron_variant		1	NM_003970.4	P1
MYOM2	ENST00000523438.1	c.715+67C>G		intron_variant		2
MYOM2	ENST00000519372.5	n.194+67C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57052 AN: 152048 Hom.: 11580 Cov.: 33

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

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.273

Gnomad4 ASJ exome AF: 0.531

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.419

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.375 AC: 57089 AN: 152166 Hom.: 11593 Cov.: 33 AF XY: 0.379 AC XY: 28171 AN XY: 74376

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.403

Alfa AF: 0.393 Hom.: 1547

Bravo AF: 0.360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2294067; hg19: chr8-2046880;