rs145736850

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_016599.5(MYOZ2):​c.561-14_561-13dupTT 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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -0.359
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
MYOZ2NM_016599.5 linkc.561-14_561-13dupTT intron_variant Intron 5 of 5 ENST00000307128.6 NP_057683.1 Q9NPC6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYOZ2ENST00000307128.6 linkc.561-23_561-22insTT intron_variant Intron 5 of 5 1 NM_016599.5 ENSP00000306997.6 Q9NPC6

Frequencies

GnomAD3 genomes
AF:
0.00465
AC:
694
AN:
149250
Hom.:
5
Cov.:
18
show subpopulations
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
show subpopulations
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
show subpopulations
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:1Other:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Dec 10, 2019
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Other:1
Aug 01, 2012
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: not provided
Review Status: no classification provided
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs112369914; hg19: chr4-120107098; API