rs719277

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.904+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,539,660 control chromosomes in the GnomAD database, including 148,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13798 hom., cov: 33)

Exomes 𝑓: 0.43 ( 134908 hom. )

Consequence

MYH2
NM_017534.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.929

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:

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=-0.85).

BP6

Variant 17-10542865-C-T is Benign according to our data. Variant chr17-10542865-C-T is described in ClinVar as [Benign]. Clinvar id is 260829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10542865-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH2	NM_017534.6 link	c.904+10G>A	intron_variant	Intron 10 of 39	ENST00000245503.10	NP_060004.3	Q9UKX2-1
MYH2	NM_001100112.2 link	c.904+10G>A	intron_variant	Intron 10 of 39		NP_001093582.1	Q9UKX2-1
MYHAS	NR_125367.1 link	n.168-24672C>T	intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10 link	c.904+10G>A		intron_variant	Intron 10 of 39	1	NM_017534.6	ENSP00000245503.5		Q9UKX2-1

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62530

AN:

151876

Hom.:

13786

Cov.:

show subpopulations

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.488

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.834

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.452

Gnomad MID

AF:

0.442

Gnomad NFE

AF:

0.403

Gnomad OTH

AF:

0.410

GnomAD3 exomes

AF:

0.486

AC:

119756

AN:

246534

Hom.:

31373

AF XY:

0.485

AC XY:

64730

AN XY:

133338

show subpopulations

Gnomad AFR exome

AF:

0.301

Gnomad AMR exome

AF:

0.598

Gnomad ASJ exome

AF:

0.452

Gnomad EAS exome

AF:

0.848

Gnomad SAS exome

AF:

0.595

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.402

Gnomad OTH exome

AF:

0.442

GnomAD4 exome

AF:

0.429

AC:

595951

AN:

1387666

Hom.:

134908

Cov.:

AF XY:

0.434

AC XY:

301360

AN XY:

694496

show subpopulations

Gnomad4 AFR exome

AF:

0.298

Gnomad4 AMR exome

AF:

0.583

Gnomad4 ASJ exome

AF:

0.452

Gnomad4 EAS exome

AF:

0.830

Gnomad4 SAS exome

AF:

0.593

Gnomad4 FIN exome

AF:

0.438

Gnomad4 NFE exome

AF:

0.397

Gnomad4 OTH exome

AF:

0.436

GnomAD4 genome

AF:

0.412

AC:

62583

AN:

151994

Hom.:

13798

Cov.:

AF XY:

0.424

AC XY:

31486

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.307

Gnomad4 AMR

AF:

0.488

Gnomad4 ASJ

AF:

0.448

Gnomad4 EAS

AF:

0.834

Gnomad4 SAS

AF:

0.616

Gnomad4 FIN

AF:

0.452

Gnomad4 NFE

AF:

0.403

Gnomad4 OTH

AF:

0.408

Alfa

AF:

0.407

Hom.:

14524

Bravo

AF:

0.407

Asia WGS

AF:

0.652

AC:

2259

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Myopathy, proximal, and ophthalmoplegia

Benign:4

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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

-0.85

CADD

Benign

0.90

DANN

Benign

0.54

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

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