rs1050113

Variant names:

• chr16-15745177-G-A
• rs1050113
• NM_002474.3:c.2472C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-15745177-G-A
• chr16-15745177-G-C
• chr16-15745177-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002474.3(MYH11):​c.2472C>T​(p.Ala824Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,613,450 control chromosomes in the GnomAD database, including 86,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A824A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.27 (6049 hom., cov: 32)
  • Exomes 𝑓: 0.33 (80739 hom.)
• Consequence: MYH11 NM_002474.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: -0.295
• Publications: 21 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 16-15745177-G-A is Benign according to our data. Variant chr16-15745177-G-A is described in ClinVar as Benign. ClinVar VariationId is 138330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.295 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3	c.2472C>T	p.Ala824Ala	synonymous_variant	Exon 20 of 41	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.2493C>T	p.Ala831Ala	synonymous_variant	Exon 21 of 43	ENST00000452625.7	NP_001035202.1
MYH11	NM_001040114.2	c.2493C>T	p.Ala831Ala	synonymous_variant	Exon 21 of 42		NP_001035203.1
MYH11	NM_022844.3	c.2472C>T	p.Ala824Ala	synonymous_variant	Exon 20 of 42		NP_074035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6	c.2472C>T	p.Ala824Ala	synonymous_variant	Exon 20 of 41	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.2493C>T	p.Ala831Ala	synonymous_variant	Exon 21 of 43	1	NM_001040113.2	ENSP00000407821.2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40622 AN: 151960 Hom.: 6050 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.260

GnomAD2 exomes AF: 0.299 AC: 75207 AN: 251320 AF XY: 0.298

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.239

Gnomad EAS exome AF: 0.402

Gnomad FIN exome AF: 0.317

Gnomad NFE exome AF: 0.331

Gnomad OTH exome AF: 0.286

GnomAD4 exome AF: 0.327 AC: 478574 AN: 1461372 Hom.: 80739 Cov.: 43 AF XY: 0.325 AC XY: 236597 AN XY: 727010

African (AFR) AF: 0.131 AC: 4390 AN: 33474

American (AMR) AF: 0.274 AC: 12240 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 6257 AN: 26134

East Asian (EAS) AF: 0.431 AC: 17086 AN: 39688

South Asian (SAS) AF: 0.251 AC: 21640 AN: 86236

European-Finnish (FIN) AF: 0.312 AC: 16664 AN: 53338

Middle Eastern (MID) AF: 0.194 AC: 1119 AN: 5766

European-Non Finnish (NFE) AF: 0.342 AC: 380326 AN: 1111646

Other (OTH) AF: 0.312 AC: 18852 AN: 60382

GnomAD4 genome AF: 0.267 AC: 40629 AN: 152078 Hom.: 6049 Cov.: 32 AF XY: 0.265 AC XY: 19710 AN XY: 74300

African (AFR) AF: 0.136 AC: 5653 AN: 41506

American (AMR) AF: 0.271 AC: 4131 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 803 AN: 3472

East Asian (EAS) AF: 0.397 AC: 2045 AN: 5146

South Asian (SAS) AF: 0.260 AC: 1251 AN: 4818

European-Finnish (FIN) AF: 0.306 AC: 3235 AN: 10582

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22776 AN: 67978

Other (OTH) AF: 0.260 AC: 548 AN: 2110

Alfa AF: 0.280 Hom.: 4765

Bravo AF: 0.260

Asia WGS AF: 0.319 AC: 1110 AN: 3478

EpiCase AF: 0.313

EpiControl AF: 0.309

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 05, 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. -

Apr 04, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ala831Ala in exon 21 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 32.2% (2769/8600) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1050113). -

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

BA1 -

Familial thoracic aortic aneurysm and aortic dissection Benign:4

Apr 08, 2019

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 16, 2018

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 19, 2015

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. -

Oct 03, 2024

All of Us Research Program, National Institutes of Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

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

- -

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

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.62
CADD	Benign	8.1
DANN	Benign	0.87
PhyloP100		-0.29
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1050113; hg19: chr16-15839034; COSMIC: COSV55543873; COSMIC: COSV55543873;