Variant 8-2057473-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000262113.9(MYOM2):c.389C>G(p.Ala130Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,613,986 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00098 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

MYOM2
ENST00000262113.9 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.919

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011306375).

BP6

Variant 8-2057473-C-G is Benign according to our data. Variant chr8-2057473-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2658306.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-2057473-C-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM2	NM_003970.4 linkuse as main transcript	c.389C>G	p.Ala130Gly	missense_variant	4/37	ENST00000262113.9	NP_003961.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOM2	ENST00000262113.9 linkuse as main transcript	c.389C>G	p.Ala130Gly	missense_variant	4/37	1	NM_003970.4	ENSP00000262113	P1
MYOM2	ENST00000523438.1 linkuse as main transcript	c.-82+12305C>G		intron_variant		2		ENSP00000428396

Frequencies

GnomAD3 genomes

AF:

0.000986

AC:

150

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00101

AC:

253

AN:

250556

Hom.:

AF XY:

0.00104

AC XY:

141

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000295

Gnomad FIN exome

AF:

0.000419

Gnomad NFE exome

AF:

0.00159

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00130

AC:

1907

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

924

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00128

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000441

Gnomad4 FIN exome

AF:

0.000618

Gnomad4 NFE exome

AF:

0.00151

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.000985

AC:

150

AN:

152288

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00159

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00105

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000832

AC:

101

EpiCase

AF:

0.00185

EpiControl

AF:

0.00190

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

MYOM2: BP4, BS2 -

MYOM2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2023

This variant is classified as likely 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

0.33

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.18

M_CAP

Benign

0.025

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.7

REVEL

Benign

0.036

Sift

Benign

0.22

Sift4G

Benign

0.14

Vest4

0.26

MVP

0.33

MPC

0.0084

ClinPred

0.0038

GERP RS

2.7

gMVP

0.34

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