chr4-119185943-G-GTT

Position:

• chr4-119185943-G-GTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_016599.5(MYOZ2):​c.561-14_561-13dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,441,644 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (5 hom., cov: 18)
  • Exomes 𝑓: 0.0020 (1 hom.)
• Consequence: MYOZ2 NM_016599.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• 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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-119185943-G-GTT is Benign according to our data. Variant chr4-119185943-G-GTT is described in ClinVar as [Likely_benign]. Clinvar id is 178659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00195 (2525/1292294) while in subpopulation AFR AF= 0.0216 (611/28226). AF 95% confidence interval is 0.0202. There are 1 homozygotes in gnomad4_exome. There are 1198 alleles in male gnomad4_exome subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 701 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOZ2	NM_016599.5	c.561-14_561-13dup		intron_variant		ENST00000307128.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOZ2	ENST00000307128.6	c.561-14_561-13dup		intron_variant		1	NM_016599.5	P1

Frequencies

GnomAD3 genomes AF: 0.00465 AC: 694 AN: 149250 Hom.: 5 Cov.: 18

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00207

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000501

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000343

Gnomad OTH AF: 0.00388

GnomAD4 exome AF: 0.00195 AC: 2525 AN: 1292294 Hom.: 1 Cov.: 26 AF XY: 0.00185 AC XY: 1198 AN XY: 646162

Gnomad4 AFR exome AF: 0.0216

Gnomad4 AMR exome AF: 0.00265

Gnomad4 ASJ exome AF: 0.00106

Gnomad4 EAS exome AF: 0.000469

Gnomad4 SAS exome AF: 0.00168

Gnomad4 FIN exome AF: 0.00150

Gnomad4 NFE exome AF: 0.00143

Gnomad4 OTH exome AF: 0.00280

GnomAD4 genome AF: 0.00469 AC: 701 AN: 149350 Hom.: 5 Cov.: 18 AF XY: 0.00454 AC XY: 330 AN XY: 72760

Gnomad4 AFR AF: 0.0155

Gnomad4 AMR AF: 0.00207

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000501

Gnomad4 NFE AF: 0.000343

Gnomad4 OTH AF: 0.00385

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 10, 2019

- -

not specified Other:1

not provided, no classification provided

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 01, 2012

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;