rs7687613

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016599.5(MYOZ2):c.459A>G(p.Glu153Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,613,936 control chromosomes in the GnomAD database, including 2,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 728 hom., cov: 31)

Exomes 𝑓: 0.033 ( 1280 hom. )

Consequence

MYOZ2
NM_016599.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 1.68

Publications

10 publications found

Variant links:

Genes affected

MYOZ2 (HGNC:1330): (myozenin 2) The protein encoded by this gene belongs to a family of sarcomeric proteins that bind to calcineurin, a phosphatase involved in calcium-dependent signal transduction in diverse cell types. These family members tether calcineurin to alpha-actinin at the z-line of the sarcomere of cardiac and skeletal muscle cells, and thus they are important for calcineurin signaling. Mutations in this gene cause cardiomyopathy familial hypertrophic type 16, a hereditary heart disorder. [provided by RefSeq, Aug 2011]

MYOZ2 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy 16
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MYOZ2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 4-119164293-A-G is Benign according to our data. Variant chr4-119164293-A-G is described in ClinVar as Benign. ClinVar VariationId is 31786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOZ2	NM_016599.5 link	c.459A>G	p.Glu153Glu	synonymous_variant	Exon 5 of 6	ENST00000307128.6	NP_057683.1	Q9NPC6
MYOZ2	NM_001440645.1 link	c.459A>G	p.Glu153Glu	synonymous_variant	Exon 5 of 7		NP_001427574.1
MYOZ2	NM_001440646.1 link	c.459A>G	p.Glu153Glu	synonymous_variant	Exon 5 of 6		NP_001427575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOZ2	ENST00000307128.6 link	c.459A>G	p.Glu153Glu	synonymous_variant	Exon 5 of 6	1	NM_016599.5	ENSP00000306997.6		Q9NPC6

Frequencies

GnomAD3 genomes

AF:

0.0698

AC:

10619

AN:

152178

Hom.:

731

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.0703

Gnomad AMR

AF:

0.0440

Gnomad ASJ

AF:

0.0361

Gnomad EAS

AF:

0.0358

Gnomad SAS

AF:

0.0577

Gnomad FIN

AF:

0.0199

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0254

Gnomad OTH

AF:

0.0592

GnomAD2 exomes

AF:

0.0424

AC:

10649

AN:

251304

AF XY:

0.0406

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.0361

Gnomad ASJ exome

AF:

0.0332

Gnomad EAS exome

AF:

0.0359

Gnomad FIN exome

AF:

0.0225

Gnomad NFE exome

AF:

0.0257

Gnomad OTH exome

AF:

0.0398

GnomAD4 exome

AF:

0.0325

AC:

47555

AN:

1461640

Hom.:

1280

Cov.:

AF XY:

0.0334

AC XY:

24271

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.177

AC:

5924

AN:

33470

American (AMR)

AF:

0.0362

AC:

1619

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0317

AC:

828

AN:

26130

East Asian (EAS)

AF:

0.0419

AC:

1664

AN:

39674

South Asian (SAS)

AF:

0.0626

AC:

5399

AN:

86248

European-Finnish (FIN)

AF:

0.0233

AC:

1246

AN:

53414

Middle Eastern (MID)

AF:

0.0749

AC:

432

AN:

5766

European-Non Finnish (NFE)

AF:

0.0251

AC:

27917

AN:

1111840

Other (OTH)

AF:

0.0418

AC:

2526

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

2339

4679

7018

9358

11697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1170

2340

3510

4680

5850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0697

AC:

10621

AN:

152296

Hom.:

728

Cov.:

AF XY:

0.0691

AC XY:

5144

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.174

AC:

7213

AN:

41538

American (AMR)

AF:

0.0440

AC:

673

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0361

AC:

125

AN:

3466

East Asian (EAS)

AF:

0.0355

AC:

184

AN:

5190

South Asian (SAS)

AF:

0.0572

AC:

276

AN:

4828

European-Finnish (FIN)

AF:

0.0199

AC:

211

AN:

10624

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0254

AC:

1726

AN:

68026

Other (OTH)

AF:

0.0600

AC:

127

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

477

953

1430

1906

2383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0420

Hom.:

458

Bravo

AF:

0.0755

Asia WGS

AF:

0.0580

AC:

201

AN:

3478

EpiCase

AF:

0.0294

EpiControl

AF:

0.0283

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Sep 22, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

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

- -

Jan 20, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1Other:1

Apr 20, 2012

Leiden Muscular Dystrophy (MYOZ2)

Significance:not provided

Review Status:no classification provided

Collection Method:curation

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hypertrophic cardiomyopathy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Jun 17, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Hypertrophic cardiomyopathy 16

Benign:1

Sep 21, 2015

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.8

(source)

DANN

Benign

0.55

PhyloP100

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over