rs2301610

Variant names:

Variant summary

Our verdict is Benign. Variant got -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:15O:1

Conservation

PhyloP100: -1.09

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 31771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-110915752-A-G is described in Lovd as [Benign].

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	UniProt
MYL2	ENST00000228841.15 link	c.132T>C	p.Ile44Ile	synonymous_variant	Exon 3 of 7	1	NM_000432.4	ENSP00000228841.8	P10916
MYL2	ENST00000663220.1 link	c.75T>C	p.Ile25Ile	synonymous_variant	Exon 3 of 7			ENSP00000499568.1	A0A590UJU8
MYL2	ENST00000548438.1 link	c.94-1428T>C		intron_variant	Intron 2 of 5	3		ENSP00000447154.1	G3V1V8

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

GnomAD3 exomes

AF:

0.101

AC:

25295

AN:

251412

Hom.:

1630

AF XY:

0.105

AC XY:

14263

AN XY:

135872

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 SAS exome

AF:

0.168

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

Gnomad4 AFR exome

AF:

0.0712

Gnomad4 AMR exome

AF:

0.0389

Gnomad4 ASJ exome

AF:

0.0369

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.166

Gnomad4 FIN exome

AF:

0.113

Gnomad4 NFE exome

AF:

0.0864

Gnomad4 OTH exome

AF:

0.0832

GnomAD4 genome

AF:

0.0854

AC:

12995

AN:

152178

Hom.:

651

Cov.:

AF XY:

0.0894

AC XY:

6652

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0709

Gnomad4 AMR

AF:

0.0547

Gnomad4 ASJ

AF:

0.0363

Gnomad4 EAS

AF:

0.211

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.112

Gnomad4 NFE

AF:

0.0850

Gnomad4 OTH

AF:

0.0564

Alfa

AF:

0.0798

Hom.:

743

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:15Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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. -

Hypertrophic cardiomyopathy 10

Benign:5

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Oct 10, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

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

- -

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

DANN

Benign

0.82

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

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