8-2144560-C-T

Position:

• chr8-2144560-C-T

Variant summary

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

The NM_003970.4(MYOM2):​c.4081-104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,141,538 control chromosomes in the GnomAD database, including 26,636 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 0.17 (2761 hom., cov: 33)
  • Exomes 𝑓: 0.21 (23875 hom.)
• Consequence: MYOM2 NM_003970.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM2	NM_003970.4	c.4081-104C>T		intron_variant		ENST00000262113.9	NP_003961.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOM2	ENST00000262113.9	c.4081-104C>T		intron_variant		1	NM_003970.4	ENSP00000262113	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26474 AN: 152032 Hom.: 2764 Cov.: 33

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.215 AC: 212345 AN: 989388 Hom.: 23875 AF XY: 0.214 AC XY: 109299 AN XY: 509952

Gnomad4 AFR exome AF: 0.0552

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.199

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.174 AC: 26468 AN: 152150 Hom.: 2761 Cov.: 33 AF XY: 0.176 AC XY: 13122 AN XY: 74388

Gnomad4 AFR AF: 0.0583

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.221

Alfa AF: 0.189 Hom.: 1521

Bravo AF: 0.167

Asia WGS AF: 0.181 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.51
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10503170; hg19: chr8-2092484;