Variant 4-119185943-G-GT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_016599.5(MYOZ2):c.561-13dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,417,560 control chromosomes in the GnomAD database, including 19,521 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6806 hom., cov: 18)

Exomes 𝑓: 0.20 ( 12715 hom. )

Consequence

MYOZ2
NM_016599.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.359

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 -16 ACMG points.

BP6

Variant 4-119185943-G-GT is Benign according to our data. Variant chr4-119185943-G-GT is described in ClinVar as [Benign]. Clinvar id is 45786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOZ2	NM_016599.5 linkuse as main transcript	c.561-13dup		intron_variant		ENST00000307128.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOZ2	ENST00000307128.6 linkuse as main transcript	c.561-13dup		intron_variant		1	NM_016599.5	P1

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42033

AN:

149150

Hom.:

6807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.469

Gnomad AMI

AF:

0.338

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.258

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.284

Gnomad NFE

AF:

0.196

Gnomad OTH

AF:

0.259

GnomAD3 exomes

AF:

0.266

AC:

48067

AN:

180466

Hom.:

2844

AF XY:

0.266

AC XY:

26061

AN XY:

97950

show subpopulations

Gnomad AFR exome

AF:

0.448

Gnomad AMR exome

AF:

0.280

Gnomad ASJ exome

AF:

0.242

Gnomad EAS exome

AF:

0.186

Gnomad SAS exome

AF:

0.291

Gnomad FIN exome

AF:

0.275

Gnomad NFE exome

AF:

0.242

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.205

AC:

259467

AN:

1268312

Hom.:

12715

Cov.:

AF XY:

0.206

AC XY:

130947

AN XY:

634288

show subpopulations

Gnomad4 AFR exome

AF:

0.416

Gnomad4 AMR exome

AF:

0.235

Gnomad4 ASJ exome

AF:

0.214

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.224

Gnomad4 NFE exome

AF:

0.192

Gnomad4 OTH exome

AF:

0.210

GnomAD4 genome

AF:

0.282

AC:

42063

AN:

149248

Hom.:

6806

Cov.:

AF XY:

0.285

AC XY:

20692

AN XY:

72698

show subpopulations

Gnomad4 AFR

AF:

0.469

Gnomad4 AMR

AF:

0.258

Gnomad4 ASJ

AF:

0.222

Gnomad4 EAS

AF:

0.158

Gnomad4 SAS

AF:

0.258

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.196

Gnomad4 OTH

AF:

0.258

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 02, 2012

Seen in large # of cases, reported in dbSNP (1000 Genomes data, no MAF) Likely Taq Slippage based on Sanger traces and does not change the ROI, so exclude from reports. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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