4-119185943-GT-G

Position:

• chr4-119185943-GT-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_016599.5(MYOZ2):​c.561-13del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000815 in 1,440,188 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 18)
  • Exomes 𝑓: 0.00090 (1 hom.)
• Consequence: MYOZ2 NM_016599.5 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 4-119185943-GT-G is Benign according to our data. Variant chr4-119185943-GT-G is described in Lovd as [Benign]. Variant chr4-119185943-GT-G is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000101 AC: 15 AN: 149248 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.000123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.000424

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000895

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000898 AC: 1159 AN: 1290840 Hom.: 1 Cov.: 26 AF XY: 0.000779 AC XY: 503 AN XY: 645840

Gnomad4 AFR exome AF: 0.000554

Gnomad4 AMR exome AF: 0.000541

Gnomad4 ASJ exome AF: 0.000254

Gnomad4 EAS exome AF: 0.000165

Gnomad4 SAS exome AF: 0.000878

Gnomad4 FIN exome AF: 0.000826

Gnomad4 NFE exome AF: 0.000978

Gnomad4 OTH exome AF: 0.000766

GnomAD4 genome AF: 0.000100 AC: 15 AN: 149348 Hom.: 0 Cov.: 18 AF XY: 0.0000825 AC XY: 6 AN XY: 72754

Gnomad4 AFR AF: 0.000122

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000391

Gnomad4 SAS AF: 0.000425

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000895

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;