8-2057506-G-A

Position:

• chr8-2057506-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000262113.9(MYOM2):​c.402+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,612,908 control chromosomes in the GnomAD database, including 102,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7650 hom., cov: 33)
  • Exomes 𝑓: 0.35 (95004 hom.)
• Consequence: MYOM2 ENST00000262113.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.44

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 8-2057506-G-A is Benign according to our data. Variant chr8-2057506-G-A is described in ClinVar as [Benign]. Clinvar id is 1231493.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM2	NM_003970.4	c.402+20G>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.402+20G>A		intron_variant		1	NM_003970.4	ENSP00000262113	P1
MYOM2	ENST00000523438.1	c.-82+12338G>A		intron_variant		2		ENSP00000428396

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44822 AN: 152018 Hom.: 7645 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.291

GnomAD3 exomes AF: 0.349 AC: 86970 AN: 248952 Hom.: 16998 AF XY: 0.342 AC XY: 46097 AN XY: 134702

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.574

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.238

Gnomad SAS exome AF: 0.288

Gnomad FIN exome AF: 0.348

Gnomad NFE exome AF: 0.355

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.354 AC: 517142 AN: 1460772 Hom.: 95004 Cov.: 71 AF XY: 0.351 AC XY: 255301 AN XY: 726642

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.555

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.277

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.365

Gnomad4 OTH exome AF: 0.320

GnomAD4 genome AF: 0.295 AC: 44839 AN: 152136 Hom.: 7650 Cov.: 33 AF XY: 0.295 AC XY: 21965 AN XY: 74360

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.287

Alfa AF: 0.282 Hom.: 1834

Bravo AF: 0.296

Asia WGS AF: 0.242 AC: 846 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 01, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.88
DANN	Benign	0.90

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: rs3765206; hg19: chr8-2005624; COSMIC: COSV50713657;