8-2057506-G-A

Variant names:

• chr8-2057506-G-A
• rs3765206
• NM_003970.4:c.402+20G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003970.4(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 NM_003970.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.44
• Publications: 6 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOM2	NM_003970.4	MANE Select	c.402+20G>A		intron	N/A	NP_003961.3	P54296

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOM2	ENST00000262113.9	TSL:1 MANE Select	c.402+20G>A		intron	N/A	ENSP00000262113.4	P54296
	MYOM2	ENST00000887732.1		c.402+20G>A		intron	N/A	ENSP00000557791.1
	MYOM2	ENST00000887733.1		c.402+20G>A		intron	N/A	ENSP00000557792.1

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

GnomAD2 exomes AF: 0.349 AC: 86970 AN: 248952 AF XY: 0.342

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 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

African (AFR) AF: 0.116 AC: 3874 AN: 33462

American (AMR) AF: 0.555 AC: 24675 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 7271 AN: 26090

East Asian (EAS) AF: 0.277 AC: 11007 AN: 39668

South Asian (SAS) AF: 0.292 AC: 25155 AN: 86154

European-Finnish (FIN) AF: 0.348 AC: 18546 AN: 53336

Middle Eastern (MID) AF: 0.220 AC: 1268 AN: 5768

European-Non Finnish (NFE) AF: 0.365 AC: 406045 AN: 1111448

Other (OTH) AF: 0.320 AC: 19301 AN: 60362

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

African (AFR) AF: 0.128 AC: 5316 AN: 41502

American (AMR) AF: 0.423 AC: 6474 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 998 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1308 AN: 5162

South Asian (SAS) AF: 0.286 AC: 1375 AN: 4814

European-Finnish (FIN) AF: 0.340 AC: 3604 AN: 10590

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24703 AN: 67984

Other (OTH) AF: 0.287 AC: 607 AN: 2114

Alfa AF: 0.299 Hom.: 3104

Bravo AF: 0.296

Asia WGS AF: 0.242 AC: 846 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.88
DANN	Benign	0.90
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: rs3765206; hg19: chr8-2005624; COSMIC: COSV50713657;