rs11559058

chr4-119135910-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 0.270

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High AC in GnomAd at 1447 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOZ2	ENST00000307128.6	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.: 10 Cov.: 32

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: 77 AN: 8284 Hom.: 2 Cov.: 0 AF XY: 0.0105 AC XY: 46 AN XY: 4392

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.: 10 Cov.: 32 AF XY: 0.00974 AC XY: 725 AN XY: 74472

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.: 7

Bravo AF: 0.00893

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1 Other: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

Other links and lift over

dbSNP: rs11559058; hg19: chr4-120057065;