8-2092276-C-T

Position:

• chr8-2092276-C-T

Variant summary

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

The ENST00000262113.9(MYOM2):​c.1829-70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,535,800 control chromosomes in the GnomAD database, including 222,808 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 0.42 (16434 hom., cov: 31)
  • Exomes 𝑓: 0.54 (206374 hom.)
• Consequence: MYOM2 ENST00000262113.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM2	NM_003970.4	c.1829-70C>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.1829-70C>T		intron_variant		1	NM_003970.4	ENSP00000262113.4
MYOM2	ENST00000523438.1	c.104-70C>T		intron_variant		2		ENSP00000428396.1
MYOM2	ENST00000518803.1	n.335-70C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63671 AN: 151868 Hom.: 16433 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.539 AC: 745845 AN: 1383814 Hom.: 206374 AF XY: 0.540 AC XY: 369951 AN XY: 685084

Gnomad4 AFR exome AF: 0.0905

Gnomad4 AMR exome AF: 0.475

Gnomad4 ASJ exome AF: 0.595

Gnomad4 EAS exome AF: 0.364

Gnomad4 SAS exome AF: 0.502

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.566

Gnomad4 OTH exome AF: 0.518

GnomAD4 genome AF: 0.419 AC: 63675 AN: 151986 Hom.: 16434 Cov.: 31 AF XY: 0.423 AC XY: 31399 AN XY: 74274

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.475

Alfa AF: 0.540 Hom.: 24437

Bravo AF: 0.404

Asia WGS AF: 0.456 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.025
DANN	Benign	0.50

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: rs2235121; hg19: chr8-2040104;