rs11721566

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 31787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-119158004-A-G is described in Lovd as [Benign]. Variant chr4-119158004-A-G is described in Lovd as [Likely_benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOZ2	NM_016599.5 link	c.247-18A>G		intron_variant	Intron 3 of 5	ENST00000307128.6	NP_057683.1	Q9NPC6
MYOZ2	XM_006714234.5 link	c.247-18A>G		intron_variant	Intron 3 of 5		XP_006714297.1

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		Q9NPC6

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

GnomAD3 exomes

AF:

0.658

AC:

165334

AN:

251202

Hom.:

55781

AF XY:

0.659

AC XY:

89532

AN XY:

135780

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 SAS exome

AF:

0.596

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

Gnomad4 AFR exome

AF:

0.311

Gnomad4 AMR exome

AF:

0.681

Gnomad4 ASJ exome

AF:

0.638

Gnomad4 EAS exome

AF:

0.567

Gnomad4 SAS exome

AF:

0.592

Gnomad4 FIN exome

AF:

0.726

Gnomad4 NFE exome

AF:

0.725

Gnomad4 OTH exome

AF:

0.669

GnomAD4 genome

AF:

0.591

AC:

89872

AN:

152050

Hom.:

28867

Cov.:

AF XY:

0.590

AC XY:

43854

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.320

Gnomad4 AMR

AF:

0.637

Gnomad4 ASJ

AF:

0.638

Gnomad4 EAS

AF:

0.612

Gnomad4 SAS

AF:

0.599

Gnomad4 FIN

AF:

0.733

Gnomad4 NFE

AF:

0.720

Gnomad4 OTH

AF:

0.609

Alfa

AF:

0.635

Hom.:

6535

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

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

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

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 20, 2012

Leiden Muscular Dystrophy (MYOZ2)

Significance: not provided

Review Status: no classification provided

Collection Method: curation

- -

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

DANN

Benign

0.55

BranchPoint Hunter

2.0

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