Variant 4-119135910-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_016599.5(MYOZ2):c.-87A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00949 in 160,594 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0095 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0093 ( 2 hom. )

Consequence

MYOZ2
NM_016599.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 0.270

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 4-119135910-A-G is Benign according to our data. Variant chr4-119135910-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 31785.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-119135910-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0095 (1447/152310) while in subpopulation SAS AF= 0.0313 (151/4826). AF 95% confidence interval is 0.0272. There are 10 homozygotes in gnomad4. There are 725 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1447 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOZ2	NM_016599.5 linkuse as main transcript	c.-87A>G		5_prime_UTR_variant	1/6	ENST00000307128.6
MYOZ2	XM_006714234.5 linkuse as main transcript	c.-87A>G		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOZ2	ENST00000307128.6 linkuse as main transcript	c.-87A>G		5_prime_UTR_variant	1/6	1	NM_016599.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00951

AC:

1447

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0311

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0139

Gnomad OTH

AF:

0.00909

GnomAD4 exome

AF:

0.00930

AC:

AN:

8284

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

AN XY:

4392

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00775

Gnomad4 ASJ exome

AF:

0.0139

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0256

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00892

Gnomad4 OTH exome

AF:

0.00281

GnomAD4 genome

AF:

0.00950

AC:

1447

AN:

152310

Hom.:

Cov.:

AF XY:

0.00974

AC XY:

725

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00238

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0313

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.0139

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.0118

Hom.:

Bravo

AF:

0.00893

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

not provided, no classification provided	curation	Leiden Muscular Dystrophy (MYOZ2)	Apr 20, 2012	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 08, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.9

DANN

Benign

0.76

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