8-2092276-C-T

Variant names:

• chr8-2092276-C-T
• rs2235121
• NM_003970.4:c.1829-70C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003970.4(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 NM_003970.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 13 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003970.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOM2	NM_003970.4	MANE Select	c.1829-70C>T		intron	N/A	NP_003961.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOM2	ENST00000262113.9	TSL:1 MANE Select	c.1829-70C>T		intron	N/A	ENSP00000262113.4
	MYOM2	ENST00000887732.1		c.1922-70C>T		intron	N/A	ENSP00000557791.1
	MYOM2	ENST00000887733.1		c.1829-70C>T		intron	N/A	ENSP00000557792.1

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

African (AFR) AF: 0.0905 AC: 2872 AN: 31746

American (AMR) AF: 0.475 AC: 19548 AN: 41142

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 13243 AN: 22266

East Asian (EAS) AF: 0.364 AC: 14251 AN: 39156

South Asian (SAS) AF: 0.502 AC: 38621 AN: 76980

European-Finnish (FIN) AF: 0.507 AC: 26131 AN: 51518

Middle Eastern (MID) AF: 0.554 AC: 3027 AN: 5460

European-Non Finnish (NFE) AF: 0.566 AC: 598429 AN: 1058204

Other (OTH) AF: 0.518 AC: 29723 AN: 57342

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

African (AFR) AF: 0.104 AC: 4324 AN: 41478

American (AMR) AF: 0.489 AC: 7469 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2051 AN: 3464

East Asian (EAS) AF: 0.400 AC: 2059 AN: 5146

South Asian (SAS) AF: 0.482 AC: 2327 AN: 4826

European-Finnish (FIN) AF: 0.513 AC: 5410 AN: 10544

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38291 AN: 67940

Other (OTH) AF: 0.475 AC: 1003 AN: 2112

Alfa AF: 0.492 Hom.: 33689

Bravo AF: 0.404

Asia WGS AF: 0.456 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.025
DANN	Benign	0.50
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2235121; hg19: chr8-2040104;