rs2294067

Variant names:

• chr8-2099050-C-G
• rs2294067
• NM_003970.4:c.2440+67C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM2	NM_003970.4	c.2440+67C>G		intron_variant	Intron 19 of 36	ENST00000262113.9	NP_003961.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOM2	ENST00000262113.9	c.2440+67C>G		intron_variant	Intron 19 of 36	1	NM_003970.4	ENSP00000262113.4
MYOM2	ENST00000523438.1	c.715+67C>G		intron_variant	Intron 6 of 23	2		ENSP00000428396.1
MYOM2	ENST00000519372.5	n.194+67C>G		intron_variant	Intron 2 of 4	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

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

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

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

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
PhyloP100		0.066

Splicing

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

Other links and lift over

dbSNP: rs2294067; hg19: chr8-2046880;