rs145736850

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-119185943-G-GT
• chr4-119185943-G-GTT
• chr4-119185943-G-GTTT
• chr4-119185943-GTTTT-G
• chr4-119185943-GT-G

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

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

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 id 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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOZ2	ENST00000307128.6	c.561-23_561-22insT		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

Gnomad4 AFR exome AF: 0.416 AC: 11953 AN: 28708

Gnomad4 AMR exome AF: 0.235 AC: 9417 AN: 39998

Gnomad4 ASJ exome AF: 0.214 AC: 4949 AN: 23118

Gnomad4 EAS exome AF: 0.191 AC: 6787 AN: 35500

Gnomad4 SAS exome AF: 0.252 AC: 19165 AN: 76062

Gnomad4 FIN exome AF: 0.224 AC: 10429 AN: 46490

Gnomad4 NFE exome AF: 0.192 AC: 184466 AN: 960652

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.469 AC: 0.468943 AN: 0.468943

Gnomad4 AMR AF: 0.258 AC: 0.257675 AN: 0.257675

Gnomad4 ASJ AF: 0.222 AC: 0.221931 AN: 0.221931

Gnomad4 EAS AF: 0.158 AC: 0.157658 AN: 0.157658

Gnomad4 SAS AF: 0.258 AC: 0.258174 AN: 0.258174

Gnomad4 FIN AF: 0.227 AC: 0.226734 AN: 0.226734

Gnomad4 NFE AF: 0.196 AC: 0.19569 AN: 0.19569

Gnomad4 OTH AF: 0.258 AC: 0.257707 AN: 0.257707

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
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

Publications

LitVar

Other links and lift over

dbSNP: rs112369914; hg19: chr4-120107098;