4-119136400-G-A

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.-14-112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 940,774 control chromosomes in the GnomAD database, including 200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (128 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (72 hom.)
• Consequence: MYOZ2 NM_016599.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.262

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=-0.85).
• BP6: Variant 4-119136400-G-A is Benign according to our data. Variant chr4-119136400-G-A is described in ClinVar as [Benign]. Clinvar id is 675767.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOZ2	NM_016599.5	c.-14-112G>A		intron_variant		ENST00000307128.6
MYOZ2	XM_006714234.5	c.-14-112G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOZ2	ENST00000307128.6	c.-14-112G>A		intron_variant		1	NM_016599.5	P1

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3403 AN: 152120 Hom.: 129 Cov.: 32

Gnomad AFR AF: 0.0743

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.00337 AC: 2656 AN: 788536 Hom.: 72 AF XY: 0.00311 AC XY: 1278 AN XY: 410500

Gnomad4 AFR exome AF: 0.0749

Gnomad4 AMR exome AF: 0.00652

Gnomad4 ASJ exome AF: 0.00630

Gnomad4 EAS exome AF: 0.0000914

Gnomad4 SAS exome AF: 0.000473

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000991

Gnomad4 OTH exome AF: 0.00792

GnomAD4 genome AF: 0.0224 AC: 3411 AN: 152238 Hom.: 128 Cov.: 32 AF XY: 0.0218 AC XY: 1622 AN XY: 74440

Gnomad4 AFR AF: 0.0743

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00118

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0130 Hom.: 11

Bravo AF: 0.0257

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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	-0.85
Cadd	Benign	1.8
Dann	Benign	0.74

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: rs78415046; hg19: chr4-120057555;