rs2272720

Variant names:

• chr8-2073341-G-T
• rs2272720
• NM_003970.4:c.961G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-2073341-G-T
• chr8-2073341-G-A
• chr8-2073341-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_003970.4(MYOM2):​c.961G>T​(p.Val321Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.399 in 1,602,956 control chromosomes in the GnomAD database, including 132,493 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.32 (9327 hom., cov: 33)
  • Exomes 𝑓: 0.41 (123166 hom.)
• Consequence: MYOM2 NM_003970.4 missense, splice_region
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.97
• Publications: 29 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0051488876).
• BP6: Variant 8-2073341-G-T is Benign according to our data. Variant chr8-2073341-G-T is described in ClinVar as Benign. ClinVar VariationId is 3060470.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.411 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.961G>T	p.Val321Leu	missense splice_region	Exon 10 of 37	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.961G>T	p.Val321Leu	missense splice_region	Exon 10 of 37	ENSP00000262113.4	P54296
	MYOM2	ENST00000887732.1		c.961G>T	p.Val321Leu	missense splice_region	Exon 10 of 38	ENSP00000557791.1
	MYOM2	ENST00000887733.1		c.961G>T	p.Val321Leu	missense splice_region	Exon 10 of 38	ENSP00000557792.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48047 AN: 151998 Hom.: 9328 Cov.: 33

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.350

GnomAD2 exomes AF: 0.385 AC: 94420 AN: 245544 AF XY: 0.392

Gnomad AFR exome AF: 0.0771

Gnomad AMR exome AF: 0.415

Gnomad ASJ exome AF: 0.498

Gnomad EAS exome AF: 0.329

Gnomad FIN exome AF: 0.362

Gnomad NFE exome AF: 0.419

Gnomad OTH exome AF: 0.397

GnomAD4 exome AF: 0.408 AC: 591271 AN: 1450842 Hom.: 123166 Cov.: 42 AF XY: 0.409 AC XY: 294916 AN XY: 720654

African (AFR) AF: 0.0705 AC: 2322 AN: 32946

American (AMR) AF: 0.407 AC: 17424 AN: 42846

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 12930 AN: 25746

East Asian (EAS) AF: 0.339 AC: 13379 AN: 39430

South Asian (SAS) AF: 0.404 AC: 34416 AN: 85278

European-Finnish (FIN) AF: 0.363 AC: 19267 AN: 53150

Middle Eastern (MID) AF: 0.458 AC: 2609 AN: 5700

European-Non Finnish (NFE) AF: 0.421 AC: 465496 AN: 1105892

Other (OTH) AF: 0.391 AC: 23428 AN: 59854

GnomAD4 genome AF: 0.316 AC: 48050 AN: 152114 Hom.: 9327 Cov.: 33 AF XY: 0.320 AC XY: 23755 AN XY: 74346

African (AFR) AF: 0.0807 AC: 3353 AN: 41542

American (AMR) AF: 0.399 AC: 6105 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1733 AN: 3470

East Asian (EAS) AF: 0.333 AC: 1711 AN: 5144

South Asian (SAS) AF: 0.366 AC: 1766 AN: 4822

European-Finnish (FIN) AF: 0.374 AC: 3952 AN: 10574

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28195 AN: 67964

Other (OTH) AF: 0.356 AC: 748 AN: 2104

Alfa AF: 0.390 Hom.: 39969

Bravo AF: 0.311

TwinsUK AF: 0.407 AC: 1509

ALSPAC AF: 0.421 AC: 1622

ESP6500AA AF: 0.0951 AC: 419

ESP6500EA AF: 0.429 AC: 3691

ExAC AF: 0.376 AC: 45698

Asia WGS AF: 0.376 AC: 1308 AN: 3478

EpiCase AF: 0.427

EpiControl AF: 0.432

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MYOM2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.94
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.16
FATHMM_MKL	Pathogenic	0.99	D
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-0.99	T
PhyloP100		6.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.14
Sift	Benign	0.28	T
Sift4G	Benign	0.095	T
Vest4		0.18
MutPred		0.41		Gain of sheet (P = 0.0827)
MPC		0.0093
ClinPred		0.023	T
GERP RS		4.6
gMVP		0.54
Mutation Taster		=88/12	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2272720; hg19: chr8-2021421; COSMIC: COSV50713274; COSMIC: COSV50713274;