Variant 8-2050864-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The ENST00000262113.9(MYOM2):c.98C>A(p.Ala33Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0215 in 1,607,738 control chromosomes in the GnomAD database, including 434 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.018 ( 43 hom., cov: 33)

Exomes 𝑓: 0.022 ( 391 hom. )

Consequence

MYOM2
ENST00000262113.9 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.91

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=0.0036394894).

BP6

Variant 8-2050864-C-A is Benign according to our data. Variant chr8-2050864-C-A is described in ClinVar as [Benign]. Clinvar id is 3060228.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr8-2050864-C-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.018 (2735/152278) while in subpopulation NFE AF= 0.0239 (1624/68016). AF 95% confidence interval is 0.0229. There are 43 homozygotes in gnomad4. There are 1346 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM2	NM_003970.4 linkuse as main transcript	c.98C>A	p.Ala33Glu	missense_variant	2/37	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.98C>A	p.Ala33Glu	missense_variant	2/37	1	NM_003970.4	ENSP00000262113	P1
MYOM2	ENST00000523438.1 linkuse as main transcript	c.-82+5696C>A		intron_variant		2		ENSP00000428396

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2736

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00767

Gnomad FIN

AF:

0.0370

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0239

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0180

AC:

4509

AN:

251052

Hom.:

AF XY:

0.0184

AC XY:

2502

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.00463

Gnomad AMR exome

AF:

0.0109

Gnomad ASJ exome

AF:

0.0347

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00906

Gnomad FIN exome

AF:

0.0305

Gnomad NFE exome

AF:

0.0233

Gnomad OTH exome

AF:

0.0206

GnomAD4 exome

AF:

0.0218

AC:

31769

AN:

1455460

Hom.:

391

Cov.:

AF XY:

0.0215

AC XY:

15556

AN XY:

722986

show subpopulations

Gnomad4 AFR exome

AF:

0.00356

Gnomad4 AMR exome

AF:

0.0115

Gnomad4 ASJ exome

AF:

0.0360

Gnomad4 EAS exome

AF:

0.0000507

Gnomad4 SAS exome

AF:

0.00954

Gnomad4 FIN exome

AF:

0.0307

Gnomad4 NFE exome

AF:

0.0238

Gnomad4 OTH exome

AF:

0.0206

GnomAD4 genome

AF:

0.0180

AC:

2735

AN:

152278

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

1346

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00431

Gnomad4 AMR

AF:

0.0199

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00747

Gnomad4 FIN

AF:

0.0370

Gnomad4 NFE

AF:

0.0239

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0179

Hom.:

Bravo

AF:

0.0167

TwinsUK

AF:

0.0191

AC:

ALSPAC

AF:

0.0205

AC:

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.0234

AC:

201

ExAC

AF:

0.0170

AC:

2062

EpiCase

AF:

0.0242

EpiControl

AF:

0.0233

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

May 30, 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.18

FATHMM_MKL

Pathogenic

0.97

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.38

PROVEAN

Benign

0.83

REVEL

Benign

0.12

Sift

Uncertain

0.011

Sift4G

Benign

0.57

Vest4

0.63

MPC

0.015

ClinPred

0.024

GERP RS

4.9

gMVP

0.65

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