17-10529321-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017534.6(MYH2):c.3263+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,611,590 control chromosomes in the GnomAD database, including 117,750 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10475 hom., cov: 32)

Exomes 𝑓: 0.37 ( 107275 hom. )

Consequence

MYH2
NM_017534.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.149

Variant links:

Genes affected

MYH2 (HGNC:7572): (myosin heavy chain 2) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in inclusion body myopathy-3. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2009]

MYH2 links:

ENSG00000272736 (HGNC:):

ENSG00000272736 links:

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MYHAS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-10529321-T-C is Benign according to our data. Variant chr17-10529321-T-C is described in ClinVar as [Benign]. Clinvar id is 260822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10529321-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH2	NM_017534.6 link	c.3263+15A>G	intron_variant	Intron 25 of 39	ENST00000245503.10	NP_060004.3	Q9UKX2-1
MYH2	NM_001100112.2 link	c.3263+15A>G	intron_variant	Intron 25 of 39		NP_001093582.1	Q9UKX2-1
MYHAS	NR_125367.1 link	n.168-38216T>C	intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10 link	c.3263+15A>G		intron_variant	Intron 25 of 39	1	NM_017534.6	ENSP00000245503.5		Q9UKX2-1

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53790

AN:

151816

Hom.:

10475

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.805

Gnomad SAS

AF:

0.494

Gnomad FIN

AF:

0.397

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.338

GnomAD3 exomes

AF:

0.428

AC:

107256

AN:

250862

Hom.:

25629

AF XY:

0.424

AC XY:

57460

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.244

Gnomad AMR exome

AF:

0.563

Gnomad ASJ exome

AF:

0.368

Gnomad EAS exome

AF:

0.826

Gnomad SAS exome

AF:

0.484

Gnomad FIN exome

AF:

0.392

Gnomad NFE exome

AF:

0.347

Gnomad OTH exome

AF:

0.386

GnomAD4 exome

AF:

0.371

AC:

542186

AN:

1459656

Hom.:

107275

Cov.:

AF XY:

0.374

AC XY:

271603

AN XY:

726178

show subpopulations

Gnomad4 AFR exome

AF:

0.241

Gnomad4 AMR exome

AF:

0.546

Gnomad4 ASJ exome

AF:

0.369

Gnomad4 EAS exome

AF:

0.802

Gnomad4 SAS exome

AF:

0.484

Gnomad4 FIN exome

AF:

0.383

Gnomad4 NFE exome

AF:

0.343

Gnomad4 OTH exome

AF:

0.376

GnomAD4 genome

AF:

0.354

AC:

53808

AN:

151934

Hom.:

10475

Cov.:

AF XY:

0.365

AC XY:

27092

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.444

Gnomad4 ASJ

AF:

0.368

Gnomad4 EAS

AF:

0.805

Gnomad4 SAS

AF:

0.493

Gnomad4 FIN

AF:

0.397

Gnomad4 NFE

AF:

0.346

Gnomad4 OTH

AF:

0.338

Alfa

AF:

0.361

Hom.:

1373

Bravo

AF:

0.353

Asia WGS

AF:

0.578

AC:

2007

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Myopathy, proximal, and ophthalmoplegia

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.6

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over