Variant 8-2052310-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003970.4(MYOM2):c.260G>T(p.Ser87Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,600,464 control chromosomes in the GnomAD database, including 1,766 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.036 ( 209 hom., cov: 33)

Exomes 𝑓: 0.020 ( 1557 hom. )

Consequence

MYOM2
NM_003970.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.463

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016503334).

BP6

Variant 8-2052310-G-T is Benign according to our data. Variant chr8-2052310-G-T is described in ClinVar as [Benign]. Clinvar id is 3060195.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOM2	NM_003970.4 linkuse as main transcript	c.260G>T	p.Ser87Ile	missense_variant	3/37	ENST00000262113.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOM2	ENST00000262113.9 linkuse as main transcript	c.260G>T	p.Ser87Ile	missense_variant	3/37	1	NM_003970.4	P1
MYOM2	ENST00000523438.1 linkuse as main transcript	c.-82+7142G>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0358

AC:

5443

AN:

152180

Hom.:

207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0972

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.0865

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00504

Gnomad OTH

AF:

0.0296

GnomAD3 exomes

AF:

0.0526

AC:

12807

AN:

243586

Hom.:

904

AF XY:

0.0465

AC XY:

6134

AN XY:

131804

show subpopulations

Gnomad AFR exome

AF:

0.0583

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.000307

Gnomad EAS exome

AF:

0.131

Gnomad SAS exome

AF:

0.0820

Gnomad FIN exome

AF:

0.0135

Gnomad NFE exome

AF:

0.00542

Gnomad OTH exome

AF:

0.0342

GnomAD4 exome

AF:

0.0199

AC:

28775

AN:

1448166

Hom.:

1557

Cov.:

AF XY:

0.0207

AC XY:

14847

AN XY:

718880

show subpopulations

Gnomad4 AFR exome

AF:

0.0579

Gnomad4 AMR exome

AF:

0.173

Gnomad4 ASJ exome

AF:

0.000425

Gnomad4 EAS exome

AF:

0.132

Gnomad4 SAS exome

AF:

0.0801

Gnomad4 FIN exome

AF:

0.0144

Gnomad4 NFE exome

AF:

0.00476

Gnomad4 OTH exome

AF:

0.0230

GnomAD4 genome

AF:

0.0358

AC:

5453

AN:

152298

Hom.:

209

Cov.:

AF XY:

0.0373

AC XY:

2779

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0578

Gnomad4 AMR

AF:

0.0976

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.0870

Gnomad4 FIN

AF:

0.0103

Gnomad4 NFE

AF:

0.00504

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0142

Hom.:

176

Bravo

AF:

0.0448

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.0506

AC:

223

ESP6500EA

AF:

0.00512

AC:

ExAC

AF:

0.0494

AC:

5999

Asia WGS

AF:

0.0900

AC:

315

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MYOM2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 23, 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

0.23

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

Cadd

Benign

0.58

Dann

Benign

0.68

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.054

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.14

REVEL

Benign

0.076

Sift

Benign

0.18

Sift4G

Benign

0.21

Vest4

0.064

MPC

0.0079

ClinPred

0.0079

GERP RS

-5.9

gMVP

0.19

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

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