4-119135991-G-GT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.696

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 -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 GnomAd at 2883 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2883 AN: 152206 Hom.: 36 Cov.: 32

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.: 1 Cov.: 0 AF XY: 0.00817 AC XY: 52 AN XY: 6366

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.: 36 Cov.: 32 AF XY: 0.0185 AC XY: 1376 AN XY: 74484

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.: 2

Bravo AF: 0.0199

Asia WGS AF: 0.00404 AC: 15 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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

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: rs58371596; hg19: chr4-120057146;