rs7661020

Variant names:

• chr4-119185827-T-C
• rs7661020
• NM_016599.5:c.561-139T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016599.5(MYOZ2):​c.561-139T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 726,368 control chromosomes in the GnomAD database, including 35,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6239 hom., cov: 32)
  • Exomes 𝑓: 0.31 (29332 hom.)
• Consequence: MYOZ2 NM_016599.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.360
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-119185827-T-C is Benign according to our data. Variant chr4-119185827-T-C is described in ClinVar as Benign. ClinVar VariationId is 674345.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOZ2	NM_016599.5	c.561-139T>C		intron_variant	Intron 5 of 5	ENST00000307128.6	NP_057683.1
MYOZ2	NM_001440645.1	c.607-139T>C		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.561-139T>C		intron_variant	Intron 5 of 5	1	NM_016599.5	ENSP00000306997.6

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41703 AN: 151980 Hom.: 6241 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.313 AC: 179599 AN: 574272 Hom.: 29332 AF XY: 0.308 AC XY: 93681 AN XY: 304186

African (AFR) AF: 0.169 AC: 2479 AN: 14626

American (AMR) AF: 0.297 AC: 7386 AN: 24854

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 3646 AN: 17662

East Asian (EAS) AF: 0.495 AC: 15751 AN: 31852

South Asian (SAS) AF: 0.217 AC: 11349 AN: 52300

European-Finnish (FIN) AF: 0.261 AC: 8191 AN: 31424

Middle Eastern (MID) AF: 0.217 AC: 495 AN: 2286

European-Non Finnish (NFE) AF: 0.329 AC: 121096 AN: 368490

Other (OTH) AF: 0.299 AC: 9206 AN: 30778

GnomAD4 genome AF: 0.274 AC: 41722 AN: 152096 Hom.: 6239 Cov.: 32 AF XY: 0.273 AC XY: 20297 AN XY: 74356

African (AFR) AF: 0.166 AC: 6904 AN: 41486

American (AMR) AF: 0.277 AC: 4242 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3464

East Asian (EAS) AF: 0.523 AC: 2712 AN: 5182

South Asian (SAS) AF: 0.230 AC: 1109 AN: 4820

European-Finnish (FIN) AF: 0.265 AC: 2806 AN: 10582

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22270 AN: 67960

Other (OTH) AF: 0.292 AC: 614 AN: 2106

Alfa AF: 0.308 Hom.: 6841

Bravo AF: 0.278

Asia WGS AF: 0.314 AC: 1090 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.81
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: rs7661020; hg19: chr4-120106982;