Variant 8-2073341-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 12/18 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). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.32 ( 9327 hom., cov: 33)

Exomes 𝑓: 0.41 ( 123166 hom. )

Consequence

MYOM2
NM_003970.4 missense, splice_region

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.97

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM2	NM_003970.4 linkuse as main transcript	c.961G>T	p.Val321Leu	missense_variant, splice_region_variant	10/37	ENST00000262113.9	NP_003961.3	P54296

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOM2	ENST00000262113.9 linkuse as main transcript	c.961G>T	p.Val321Leu	missense_variant, splice_region_variant	10/37	1	NM_003970.4	ENSP00000262113.4		P54296
MYOM2	ENST00000523438.1 linkuse as main transcript	c.-81-16667G>T		intron_variant		2		ENSP00000428396.1		E7EWH9

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

48047

AN:

151998

Hom.:

9328

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.385

AC:

94420

AN:

245544

Hom.:

19201

AF XY:

0.392

AC XY:

52190

AN XY:

132986

show subpopulations

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 SAS exome

AF:

0.398

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.:

AF XY:

0.409

AC XY:

294916

AN XY:

720654

show subpopulations

Gnomad4 AFR exome

AF:

0.0705

Gnomad4 AMR exome

AF:

0.407

Gnomad4 ASJ exome

AF:

0.502

Gnomad4 EAS exome

AF:

0.339

Gnomad4 SAS exome

AF:

0.404

Gnomad4 FIN exome

AF:

0.363

Gnomad4 NFE exome

AF:

0.421

Gnomad4 OTH exome

AF:

0.391

GnomAD4 genome

AF:

0.316

AC:

48050

AN:

152114

Hom.:

9327

Cov.:

AF XY:

0.320

AC XY:

23755

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0807

Gnomad4 AMR

AF:

0.399

Gnomad4 ASJ

AF:

0.499

Gnomad4 EAS

AF:

0.333

Gnomad4 SAS

AF:

0.366

Gnomad4 FIN

AF:

0.374

Gnomad4 NFE

AF:

0.415

Gnomad4 OTH

AF:

0.356

Alfa

AF:

0.412

Hom.:

26275

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

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MYOM2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.94

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.16

FATHMM_MKL

Pathogenic

0.99

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.99

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.4

REVEL

Benign

0.14

Sift

Benign

0.28

Sift4G

Benign

0.095

Vest4

0.18

MutPred

0.41

Gain of sheet (P = 0.0827);

MPC

0.0093

ClinPred

0.023

GERP RS

4.6

gMVP

0.54

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over