rs1042236

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017534.6(MYH2):c.5034C>T(p.Ala1678Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,613,808 control chromosomes in the GnomAD database, including 39,588 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3900 hom., cov: 33)

Exomes 𝑓: 0.19 ( 35688 hom. )

Consequence

MYH2
NM_017534.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

MYH2 (HGNC:7572): (myosin heavy chain 2) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in inclusion body myopathy-3. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2009]

MYH2 links:

ENSG00000272736 (HGNC:):

ENSG00000272736 links:

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MYHAS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 17-10524607-G-A is Benign according to our data. Variant chr17-10524607-G-A is described in ClinVar as [Benign]. Clinvar id is 260826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10524607-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH2	NM_017534.6 link	c.5034C>T	p.Ala1678Ala	synonymous_variant	Exon 35 of 40	ENST00000245503.10	NP_060004.3	Q9UKX2-1
MYH2	NM_001100112.2 link	c.5034C>T	p.Ala1678Ala	synonymous_variant	Exon 35 of 40		NP_001093582.1	Q9UKX2-1
MYHAS	NR_125367.1 link	n.168-42930G>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10 link	c.5034C>T	p.Ala1678Ala	synonymous_variant	Exon 35 of 40	1	NM_017534.6	ENSP00000245503.5		Q9UKX2-1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28453

AN:

152020

Hom.:

3897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.178

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.732

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.208

Gnomad MID

AF:

0.197

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.181

GnomAD3 exomes

AF:

0.266

AC:

66885

AN:

251154

Hom.:

13128

AF XY:

0.257

AC XY:

34862

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.475

Gnomad ASJ exome

AF:

0.204

Gnomad EAS exome

AF:

0.751

Gnomad SAS exome

AF:

0.315

Gnomad FIN exome

AF:

0.202

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.219

GnomAD4 exome

AF:

0.186

AC:

272221

AN:

1461668

Hom.:

35688

Cov.:

AF XY:

0.189

AC XY:

137073

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.102

Gnomad4 AMR exome

AF:

0.454

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.741

Gnomad4 SAS exome

AF:

0.316

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.146

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.187

AC:

28471

AN:

152140

Hom.:

3900

Cov.:

AF XY:

0.198

AC XY:

14710

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.313

Gnomad4 ASJ

AF:

0.215

Gnomad4 EAS

AF:

0.731

Gnomad4 SAS

AF:

0.327

Gnomad4 FIN

AF:

0.208

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.158

Hom.:

909

Bravo

AF:

0.195

Asia WGS

AF:

0.471

AC:

1635

AN:

3476

EpiCase

AF:

0.152

EpiControl

AF:

0.148

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 25, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Myopathy, proximal, and ophthalmoplegia

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

7.3

DANN

Benign

0.80

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