rs7661020

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.81).
• BP6: Variant 4-119185827-T-C is Benign according to our data. Variant chr4-119185827-T-C is described in ClinVar as [Benign]. Clinvar id 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

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

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.495

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.329

Gnomad4 OTH exome AF: 0.299

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

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.292

Alfa AF: 0.303 Hom.: 4007

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

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: rs7661020; hg19: chr4-120106982;