NM_000432.4:c.274+25_274+26dupGT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000432.4(MYL2):c.274+25_274+26dupGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 1,369,570 control chromosomes in the GnomAD database, including 1,729 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 549 hom., cov: 31)

Exomes 𝑓: 0.076 ( 1180 hom. )

Consequence

MYL2
NM_000432.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.360

Publications

2 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 -16 ACMG points.

BP6

Variant 12-110914159-G-GAC is Benign according to our data. Variant chr12-110914159-G-GAC is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYL2	NM_000432.4 link	c.274+25_274+26dupGT	intron_variant	Intron 4 of 6	ENST00000228841.15	NP_000423.2	P10916Q6IB42
MYL2	NM_001406745.1 link	c.232+25_232+26dupGT	intron_variant	Intron 3 of 5		NP_001393674.1
MYL2	NM_001406916.1 link	c.217+25_217+26dupGT	intron_variant	Intron 4 of 6		NP_001393845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL2	ENST00000228841.15 link	c.274+26_274+27insGT		intron_variant	Intron 4 of 6	1	NM_000432.4	ENSP00000228841.8		P10916

Frequencies

GnomAD3 genomes

AF:

0.0776

AC:

11644

AN:

149990

Hom.:

550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0819

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0457

Gnomad ASJ

AF:

0.0351

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.0682

Gnomad MID

AF:

0.0649

Gnomad NFE

AF:

0.0702

Gnomad OTH

AF:

0.0533

GnomAD2 exomes

AF:

0.178

AC:

20713

AN:

116462

AF XY:

0.186

show subpopulations

Gnomad AFR exome

AF:

0.168

Gnomad AMR exome

AF:

0.0751

Gnomad ASJ exome

AF:

0.0860

Gnomad EAS exome

AF:

0.338

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.0764

AC:

93138

AN:

1219476

Hom.:

1180

Cov.:

AF XY:

0.0794

AC XY:

48757

AN XY:

613876

show subpopulations

African (AFR)

AF:

0.0809

AC:

2295

AN:

28370

American (AMR)

AF:

0.0336

AC:

1393

AN:

41412

Ashkenazi Jewish (ASJ)

AF:

0.0365

AC:

851

AN:

23334

East Asian (EAS)

AF:

0.209

AC:

7626

AN:

36568

South Asian (SAS)

AF:

0.152

AC:

11816

AN:

77864

European-Finnish (FIN)

AF:

0.0721

AC:

3567

AN:

49480

Middle Eastern (MID)

AF:

0.0564

AC:

292

AN:

5174

European-Non Finnish (NFE)

AF:

0.0680

AC:

61632

AN:

905792

Other (OTH)

AF:

0.0712

AC:

3666

AN:

51482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

4285

8569

12854

17138

21423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2286

4572

6858

9144

11430

<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:

0.0776

AC:

11645

AN:

150094

Hom.:

549

Cov.:

AF XY:

0.0801

AC XY:

5859

AN XY:

73186

show subpopulations

African (AFR)

AF:

0.0820

AC:

3359

AN:

40966

American (AMR)

AF:

0.0456

AC:

685

AN:

15034

Ashkenazi Jewish (ASJ)

AF:

0.0351

AC:

121

AN:

3444

East Asian (EAS)

AF:

0.212

AC:

1091

AN:

5136

South Asian (SAS)

AF:

0.164

AC:

775

AN:

4726

European-Finnish (FIN)

AF:

0.0682

AC:

695

AN:

10186

Middle Eastern (MID)

AF:

0.0664

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0702

AC:

4727

AN:

67336

Other (OTH)

AF:

0.0522

AC:

108

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

510

1021

1531

2042

2552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<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:

0.0343

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 26, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

274+26_274+27insGT in intron 4 of MYL2: This variant is not expected to have cl inical or pathological significance because it does not alter an amino acid resi due and is not located in the highly conserved region of the 5' splice site. -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Cardiomyopathy

Benign:1

Sep 30, 2020

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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