chr4-119185943-G-GT

Variant names:

• chr4-119185943-G-GT
• rs112369914
• NM_016599.5:c.561-13dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_016599.5(MYOZ2):​c.561-13dupT 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.359
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy 16

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MYOZ2	NM_016599.5	c.561-13dupT		intron_variant	Intron 5 of 5	ENST00000307128.6	NP_057683.1
MYOZ2	NM_001440645.1	c.607-13dupT		intron_variant	Intron 6 of 6		NP_001427574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOZ2	ENST00000307128.6	c.561-13dupT		intron_variant	Intron 5 of 5	1	NM_016599.5	ENSP00000306997.6

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42033 AN: 149150 Hom.: 6807 Cov.: 18

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

GnomAD2 exomes AF: 0.266 AC: 48067 AN: 180466 AF XY: 0.266

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 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.: 26 AF XY: 0.206 AC XY: 130947 AN XY: 634288

African (AFR) AF: 0.416 AC: 11953 AN: 28708

American (AMR) AF: 0.235 AC: 9417 AN: 39998

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 4949 AN: 23118

East Asian (EAS) AF: 0.191 AC: 6787 AN: 35500

South Asian (SAS) AF: 0.252 AC: 19165 AN: 76062

European-Finnish (FIN) AF: 0.224 AC: 10429 AN: 46490

Middle Eastern (MID) AF: 0.243 AC: 1268 AN: 5226

European-Non Finnish (NFE) AF: 0.192 AC: 184466 AN: 960652

Other (OTH) AF: 0.210 AC: 11033 AN: 52558

GnomAD4 genome AF: 0.282 AC: 42063 AN: 149248 Hom.: 6806 Cov.: 18 AF XY: 0.285 AC XY: 20692 AN XY: 72698

African (AFR) AF: 0.469 AC: 19131 AN: 40796

American (AMR) AF: 0.258 AC: 3861 AN: 14984

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 763 AN: 3438

East Asian (EAS) AF: 0.158 AC: 805 AN: 5106

South Asian (SAS) AF: 0.258 AC: 1216 AN: 4710

European-Finnish (FIN) AF: 0.227 AC: 2256 AN: 9950

Middle Eastern (MID) AF: 0.282 AC: 80 AN: 284

European-Non Finnish (NFE) AF: 0.196 AC: 13112 AN: 67004

Other (OTH) AF: 0.258 AC: 535 AN: 2076

Alfa AF: 0.148 Hom.: 221

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Feb 02, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Oct 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs112369914; hg19: chr4-120107098;