rs2280902

Positions:

• chr8-2129084-G-A
• chr8-2129084-G-C
• chr8-2129084-G-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MYOM2	NM_003970.4	c.3695-43G>A		intron_variant		ENST00000262113.9	NP_003961.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOM2	ENST00000262113.9	c.3695-43G>A		intron_variant		1	NM_003970.4	ENSP00000262113.4

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60548 AN: 151902 Hom.: 12375 Cov.: 32

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.: 17 AF XY: 0.438 AC XY: 276237 AN XY: 630732

Gnomad4 AFR exome AF: 0.305

Gnomad4 AMR exome AF: 0.424

Gnomad4 ASJ exome AF: 0.518

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.463

Gnomad4 OTH exome AF: 0.437

GnomAD4 genome AF: 0.398 AC: 60561 AN: 152020 Hom.: 12372 Cov.: 32 AF XY: 0.394 AC XY: 29283 AN XY: 74332

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.386

Alfa AF: 0.447 Hom.: 12013

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2280902; hg19: chr8-2077072;