rs2301610

Variant names:

Variant summary

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

The NM_000432.4(MYL2):c.132T>C(p.Ile44Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 1,613,832 control chromosomes in the GnomAD database, including 7,752 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 651 hom., cov: 32)

Exomes 𝑓: 0.093 ( 7101 hom. )

Consequence

MYL2
NM_000432.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:16O:1

Conservation

PhyloP100: -1.09

Publications

30 publications found

Variant links:

Genes affected

MYL2 (HGNC:7583): (myosin light chain 2) This gene encodes a major sarcomeric protein in mammalian striated muscle. The encoded protein plays a role in embryonic heart muscle structure and function, while phosphorylation of the encoded protein is involved in cardiac myosin cycling kinetics, torsion and function in adults. Mutations in this gene are associated with hypertrophic cardiomyopathy 10 and infant-onset myopathy. [provided by RefSeq, May 2022]

MYL2 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 10
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
congenital fiber-type disproportion myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MYL2 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=-0.51).

BP6

Variant 12-110915752-A-G is Benign according to our data. Variant chr12-110915752-A-G is described in ClinVar as Benign. ClinVar VariationId is 31771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL2	NM_000432.4 link	c.132T>C	p.Ile44Ile	synonymous_variant	Exon 3 of 7	ENST00000228841.15	NP_000423.2	P10916Q6IB42
MYL2	NM_001406916.1 link	c.75T>C	p.Ile25Ile	synonymous_variant	Exon 3 of 7		NP_001393845.1
MYL2	NM_001406745.1 link	c.94-1428T>C		intron_variant	Intron 2 of 5		NP_001393674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL2	ENST00000228841.15 link	c.132T>C	p.Ile44Ile	synonymous_variant	Exon 3 of 7	1	NM_000432.4	ENSP00000228841.8		P10916

Frequencies

GnomAD3 genomes

AF:

0.0854

AC:

12992

AN:

152060

Hom.:

651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0708

Gnomad AMI

AF:

0.0747

Gnomad AMR

AF:

0.0549

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0850

Gnomad OTH

AF:

0.0575

GnomAD2 exomes

AF:

0.101

AC:

25295

AN:

251412

AF XY:

0.105

show subpopulations

Gnomad AFR exome

AF:

0.0696

Gnomad AMR exome

AF:

0.0386

Gnomad ASJ exome

AF:

0.0354

Gnomad EAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.0871

Gnomad OTH exome

AF:

0.0870

GnomAD4 exome

AF:

0.0928

AC:

135614

AN:

1461654

Hom.:

7101

Cov.:

AF XY:

0.0953

AC XY:

69306

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.0712

AC:

2382

AN:

33470

American (AMR)

AF:

0.0389

AC:

1738

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0369

AC:

965

AN:

26136

East Asian (EAS)

AF:

0.221

AC:

8771

AN:

39690

South Asian (SAS)

AF:

0.166

AC:

14284

AN:

86252

European-Finnish (FIN)

AF:

0.113

AC:

6021

AN:

53416

Middle Eastern (MID)

AF:

0.0648

AC:

374

AN:

5768

European-Non Finnish (NFE)

AF:

0.0864

AC:

96056

AN:

1111806

Other (OTH)

AF:

0.0832

AC:

5023

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

6989

13979

20968

27958

34947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3676

7352

11028

14704

18380

<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:

0.0854

AC:

12995

AN:

152178

Hom.:

651

Cov.:

AF XY:

0.0894

AC XY:

6652

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0709

AC:

2946

AN:

41530

American (AMR)

AF:

0.0547

AC:

837

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0363

AC:

126

AN:

3470

East Asian (EAS)

AF:

0.211

AC:

1092

AN:

5168

South Asian (SAS)

AF:

0.169

AC:

815

AN:

4818

European-Finnish (FIN)

AF:

0.112

AC:

1187

AN:

10582

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0850

AC:

5783

AN:

68006

Other (OTH)

AF:

0.0564

AC:

119

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

593

1186

1780

2373

2966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.0820

Hom.:

1734

Bravo

AF:

0.0778

Asia WGS

AF:

0.125

AC:

432

AN:

3478

EpiCase

AF:

0.0791

EpiControl

AF:

0.0784

ClinVar

Significance: Benign

Submissions summary: Benign:16Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

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

- -

Jan 18, 2008

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 27, 2011

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. -

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

- -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Hypertrophic cardiomyopathy 10

Benign:5

Mar 06, 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. -

Oct 10, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2Other:1

Mar 26, 2012

Leiden Muscular Dystrophy (MYL2)

Significance:not provided

Review Status:no classification provided

Collection Method:curation

- -

Nov 19, 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

- -

Cardiomyopathy

Benign:1

Mar 16, 2018

Color Diagnostics, LLC DBA Color Health

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congestive heart failure

Benign:1

Oct 10, 2022

Cohesion Phenomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Jun 29, 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: seen in unaffected individuals, 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

-0.51

CADD

Benign

3.0

(source)

DANN

Benign

0.82

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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