rs11721566

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016599.5(MYOZ2):c.247-18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 1,612,922 control chromosomes in the GnomAD database, including 388,515 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.59 ( 28867 hom., cov: 31)

Exomes 𝑓: 0.70 ( 359648 hom. )

Consequence

MYOZ2
NM_016599.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: -0.374

Publications

12 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 -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 4-119158004-A-G is Benign according to our data. Variant chr4-119158004-A-G is described in ClinVar as Benign. ClinVar VariationId is 31787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MYOZ2	NM_016599.5 link	c.247-18A>G	intron_variant	Intron 3 of 5	ENST00000307128.6	NP_057683.1
MYOZ2	NM_001440645.1 link	c.247-18A>G	intron_variant	Intron 3 of 6		NP_001427574.1
MYOZ2	NM_001440646.1 link	c.247-18A>G	intron_variant	Intron 3 of 5		NP_001427575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOZ2	ENST00000307128.6 link	c.247-18A>G		intron_variant	Intron 3 of 5	1	NM_016599.5	ENSP00000306997.6

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89812

AN:

151932

Hom.:

28844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.637

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.599

Gnomad FIN

AF:

0.733

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.608

GnomAD2 exomes

AF:

0.658

AC:

165334

AN:

251202

AF XY:

0.659

show subpopulations

Gnomad AFR exome

AF:

0.311

Gnomad AMR exome

AF:

0.687

Gnomad ASJ exome

AF:

0.640

Gnomad EAS exome

AF:

0.621

Gnomad FIN exome

AF:

0.731

Gnomad NFE exome

AF:

0.710

Gnomad OTH exome

AF:

0.656

GnomAD4 exome

AF:

0.697

AC:

1018423

AN:

1460872

Hom.:

359648

Cov.:

AF XY:

0.694

AC XY:

504125

AN XY:

726762

show subpopulations

African (AFR)

AF:

0.311

AC:

10397

AN:

33442

American (AMR)

AF:

0.681

AC:

30449

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

16655

AN:

26120

East Asian (EAS)

AF:

0.567

AC:

22482

AN:

39678

South Asian (SAS)

AF:

0.592

AC:

51066

AN:

86222

European-Finnish (FIN)

AF:

0.726

AC:

38775

AN:

53378

Middle Eastern (MID)

AF:

0.495

AC:

2854

AN:

5766

European-Non Finnish (NFE)

AF:

0.725

AC:

805364

AN:

1111222

Other (OTH)

AF:

0.669

AC:

40381

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

14317

28634

42952

57269

71586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19872

39744

59616

79488

99360

<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:

0.591

AC:

89872

AN:

152050

Hom.:

28867

Cov.:

AF XY:

0.590

AC XY:

43854

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.320

AC:

13268

AN:

41458

American (AMR)

AF:

0.637

AC:

9730

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

2214

AN:

3470

East Asian (EAS)

AF:

0.612

AC:

3151

AN:

5150

South Asian (SAS)

AF:

0.599

AC:

2891

AN:

4824

European-Finnish (FIN)

AF:

0.733

AC:

7745

AN:

10570

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.720

AC:

48973

AN:

67992

Other (OTH)

AF:

0.609

AC:

1288

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1655

3311

4966

6622

8277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

738

1476

2214

2952

3690

<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:

0.644

Hom.:

11455

Bravo

AF:

0.576

Asia WGS

AF:

0.625

AC:

2177

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 08, 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. -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Hypertrophic cardiomyopathy 16

Benign:3

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.55

PhyloP100

-0.37

BranchPoint Hunter

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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