Variant 8-2052291-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003970.4(MYOM2):c.241G>A(p.Glu81Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,605,502 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. 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 0.012 ( 16 hom., cov: 33)

Exomes 𝑓: 0.015 ( 232 hom. )

Consequence

MYOM2
NM_003970.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.42

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=0.0039822757).

BP6

Variant 8-2052291-G-A is Benign according to our data. Variant chr8-2052291-G-A is described in ClinVar as [Benign]. Clinvar id is 3056560.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr8-2052291-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0118 (1803/152332) while in subpopulation SAS AF= 0.0286 (138/4826). AF 95% confidence interval is 0.0247. There are 16 homozygotes in gnomad4. There are 927 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM2	NM_003970.4 linkuse as main transcript	c.241G>A	p.Glu81Lys	missense_variant	3/37	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.241G>A	p.Glu81Lys	missense_variant	3/37	1	NM_003970.4	ENSP00000262113.4		P54296
MYOM2	ENST00000523438.1 linkuse as main transcript	c.-82+7123G>A		intron_variant		2		ENSP00000428396.1		E7EWH9

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1800

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00707

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0284

Gnomad FIN

AF:

0.0241

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0162

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0159

AC:

3898

AN:

245550

Hom.:

AF XY:

0.0175

AC XY:

2329

AN XY:

132720

show subpopulations

Gnomad AFR exome

AF:

0.00205

Gnomad AMR exome

AF:

0.00624

Gnomad ASJ exome

AF:

0.0170

Gnomad EAS exome

AF:

0.0000552

Gnomad SAS exome

AF:

0.0350

Gnomad FIN exome

AF:

0.0242

Gnomad NFE exome

AF:

0.0163

Gnomad OTH exome

AF:

0.0200

GnomAD4 exome

AF:

0.0151

AC:

21919

AN:

1453170

Hom.:

232

Cov.:

AF XY:

0.0157

AC XY:

11309

AN XY:

722034

show subpopulations

Gnomad4 AFR exome

AF:

0.00259

Gnomad4 AMR exome

AF:

0.00670

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.0000507

Gnomad4 SAS exome

AF:

0.0334

Gnomad4 FIN exome

AF:

0.0234

Gnomad4 NFE exome

AF:

0.0144

Gnomad4 OTH exome

AF:

0.0157

GnomAD4 genome

AF:

0.0118

AC:

1803

AN:

152332

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

927

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00216

Gnomad4 AMR

AF:

0.00706

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0286

Gnomad4 FIN

AF:

0.0241

Gnomad4 NFE

AF:

0.0162

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0141

Hom.:

Bravo

AF:

0.00925

TwinsUK

AF:

0.0140

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.0185

AC:

159

ExAC

AF:

0.0163

AC:

1974

Asia WGS

AF:

0.0110

AC:

AN:

3478

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

Mar 07, 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

0.15

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.61

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.75

REVEL

Benign

0.077

Sift

Benign

0.46

Sift4G

Benign

0.26

Vest4

0.47

MPC

0.0076

ClinPred

0.011

GERP RS

3.8

gMVP

0.29

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