rs587781046

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002474.3(MYH11):c.2061C>T(p.Ser687Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 1,613,574 control chromosomes in the GnomAD database, including 4,133 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 335 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3798 hom. )

Consequence

MYH11
NM_002474.3 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: -3.89

Publications

14 publications found

Variant links:

Genes affected

MYH11 (HGNC:7569): (myosin heavy chain 11) The protein encoded by this gene is a smooth muscle myosin belonging to the myosin heavy chain family. The gene product is a subunit of a hexameric protein that consists of two heavy chain subunits and two pairs of non-identical light chain subunits. It functions as a major contractile protein, converting chemical energy into mechanical energy through the hydrolysis of ATP. A chromosomal rearrangement involving this gene is associated with acute myeloid leukemia of the M4Eo subtype. Mutations in this gene are associated with visceral myopathy, megacystis-microcolon-intestinal hypoperistalsis syndrome 2, and familial thoracic aortic aneurysm 4. [provided by RefSeq, May 2022]

MYH11 Gene-Disease associations (from GenCC):

familial thoracic aortic aneurysm and aortic dissection
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
aortic aneurysm, familial thoracic 4
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
megacystis-microcolon-intestinal hypoperistalsis syndrome 2
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
megacystis-microcolon-intestinal hypoperistalsis syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
visceral myopathy 2
Inheritance: AR, AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

MYH11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 16-15748166-G-A is Benign according to our data. Variant chr16-15748166-G-A is described in ClinVar as Benign. ClinVar VariationId is 138328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.89 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
MYH11	NM_002474.3 link	c.2061C>T	p.Ser687Ser	splice_region_variant, synonymous_variant	Exon 17 of 41	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2 link	c.2082C>T	p.Ser694Ser	splice_region_variant, synonymous_variant	Exon 18 of 43	ENST00000452625.7	NP_001035202.1
MYH11	NM_001040114.2 link	c.2082C>T	p.Ser694Ser	splice_region_variant, synonymous_variant	Exon 18 of 42		NP_001035203.1
MYH11	NM_022844.3 link	c.2061C>T	p.Ser687Ser	splice_region_variant, synonymous_variant	Exon 17 of 42		NP_074035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6 link	c.2061C>T	p.Ser687Ser	splice_region_variant, synonymous_variant	Exon 17 of 41	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7 link	c.2082C>T	p.Ser694Ser	splice_region_variant, synonymous_variant	Exon 18 of 43	1	NM_001040113.2	ENSP00000407821.2

Frequencies

GnomAD3 genomes

AF:

0.0630

AC:

9583

AN:

152160

Hom.:

337

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0542

Gnomad AMI

AF:

0.0341

Gnomad AMR

AF:

0.0461

Gnomad ASJ

AF:

0.0853

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.0706

Gnomad FIN

AF:

0.0281

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0677

Gnomad OTH

AF:

0.0692

GnomAD2 exomes

AF:

0.0649

AC:

16247

AN:

250184

AF XY:

0.0660

show subpopulations

Gnomad AFR exome

AF:

0.0512

Gnomad AMR exome

AF:

0.0277

Gnomad ASJ exome

AF:

0.0902

Gnomad EAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.0296

Gnomad NFE exome

AF:

0.0634

Gnomad OTH exome

AF:

0.0644

GnomAD4 exome

AF:

0.0678

AC:

99136

AN:

1461296

Hom.:

3798

Cov.:

AF XY:

0.0680

AC XY:

49460

AN XY:

726944

show subpopulations

African (AFR)

AF:

0.0528

AC:

1766

AN:

33478

American (AMR)

AF:

0.0304

AC:

1358

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0894

AC:

2336

AN:

26136

East Asian (EAS)

AF:

0.152

AC:

6045

AN:

39696

South Asian (SAS)

AF:

0.0646

AC:

5568

AN:

86258

European-Finnish (FIN)

AF:

0.0307

AC:

1623

AN:

52842

Middle Eastern (MID)

AF:

0.0654

AC:

377

AN:

5768

European-Non Finnish (NFE)

AF:

0.0677

AC:

75337

AN:

1112002

Other (OTH)

AF:

0.0783

AC:

4726

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

6543

13086

19630

26173

32716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2906

5812

8718

11624

14530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0630

AC:

9586

AN:

152278

Hom.:

335

Cov.:

AF XY:

0.0606

AC XY:

4513

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0542

AC:

2254

AN:

41560

American (AMR)

AF:

0.0460

AC:

704

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0853

AC:

296

AN:

3472

East Asian (EAS)

AF:

0.173

AC:

897

AN:

5172

South Asian (SAS)

AF:

0.0702

AC:

339

AN:

4826

European-Finnish (FIN)

AF:

0.0281

AC:

299

AN:

10622

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0676

AC:

4600

AN:

68012

Other (OTH)

AF:

0.0681

AC:

144

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

475

950

1425

1900

2375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0659

Hom.:

243

Bravo

AF:

0.0638

Asia WGS

AF:

0.117

AC:

407

AN:

3478

EpiCase

AF:

0.0677

EpiControl

AF:

0.0616

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 04, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ser694Ser in exon 18 of MYH11: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 6.7% (576/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs880071). -

Nov 16, 2012

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:3

Feb 05, 2024

All of Us Research Program, National Institutes of Health

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 07, 2018

Color Diagnostics, LLC DBA Color Health

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 26, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene -

Aortic aneurysm, familial thoracic 4

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

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. -

not provided

Benign:2

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Visceral myopathy 2

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Megacystis-microcolon-intestinal hypoperistalsis syndrome 2

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Nov 24, 2014

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.0040

(source)

DANN

Benign

0.46

PhyloP100

-3.9

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over