Variant 4-119135991-G-GT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_016599.5(MYOZ2):c.-15+11dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 164,364 control chromosomes in the GnomAD database, including 37 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 36 hom., cov: 32)

Exomes 𝑓: 0.0087 ( 1 hom. )

Consequence

MYOZ2
NM_016599.5 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.696

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 4-119135991-G-GT is Benign according to our data. Variant chr4-119135991-G-GT is described in ClinVar as [Likely_benign]. Clinvar id is 347405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.019 (2887/152324) while in subpopulation AFR AF= 0.036 (1495/41568). AF 95% confidence interval is 0.0344. There are 36 homozygotes in gnomad4. There are 1376 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2887 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOZ2	NM_016599.5 linkuse as main transcript	c.-15+11dup		intron_variant		ENST00000307128.6
MYOZ2	XM_006714234.5 linkuse as main transcript	c.-15+11dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOZ2	ENST00000307128.6 linkuse as main transcript	c.-15+11dup		intron_variant		1	NM_016599.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2883

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0359

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00621

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0146

Gnomad OTH

AF:

0.0162

GnomAD4 exome

AF:

0.00872

AC:

105

AN:

12040

Hom.:

Cov.:

AF XY:

0.00817

AC XY:

AN XY:

6366

show subpopulations

Gnomad4 AFR exome

AF:

0.0152

Gnomad4 AMR exome

AF:

0.00543

Gnomad4 ASJ exome

AF:

0.00676

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00240

Gnomad4 FIN exome

AF:

0.00331

Gnomad4 NFE exome

AF:

0.0114

Gnomad4 OTH exome

AF:

0.00943

GnomAD4 genome

AF:

0.0190

AC:

2887

AN:

152324

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1376

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0360

Gnomad4 AMR

AF:

0.0135

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00621

Gnomad4 NFE

AF:

0.0146

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0165

Hom.:

Bravo

AF:

0.0199

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Hypertrophic cardiomyopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hypertrophic cardiomyopathy 16

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 27, 2021

- -

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