12-110913199-AG-AGG

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.353+46dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0773 in 1,593,392 control chromosomes in the GnomAD database, including 5,554 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 495 hom., cov: 32)

Exomes 𝑓: 0.077 ( 5059 hom. )

Consequence

MYL2
NM_000432.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -0.228

Publications

6 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 12-110913199-A-AG is Benign according to our data. Variant chr12-110913199-A-AG is described in ClinVar as Benign. ClinVar VariationId is 31775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000432.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYL2	NM_000432.4	MANE Select	c.353+46dupC	intron	N/A	NP_000423.2
MYL2	NM_001406745.1		c.311+46dupC	intron	N/A	NP_001393674.1
MYL2	NM_001406916.1		c.296+46dupC	intron	N/A	NP_001393845.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYL2	ENST00000228841.15	TSL:1 MANE Select	c.353+46dupC	intron	N/A	ENSP00000228841.8
MYL2	ENST00000549029.1	TSL:2	n.230dupC	non_coding_transcript_exon	Exon 2 of 2
MYL2	ENST00000713800.1		c.353+46dupC	intron	N/A	ENSP00000519106.1

Frequencies

GnomAD3 genomes

AF:

0.0784

AC:

11027

AN:

140630

Hom.:

496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0873

Gnomad AMI

AF:

0.0734

Gnomad AMR

AF:

0.0479

Gnomad ASJ

AF:

0.0346

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.0691

Gnomad MID

AF:

0.0649

Gnomad NFE

AF:

0.0706

Gnomad OTH

AF:

0.0515

GnomAD2 exomes

AF:

0.0742

AC:

18258

AN:

245936

AF XY:

0.0778

show subpopulations

Gnomad AFR exome

AF:

0.0576

Gnomad AMR exome

AF:

0.0237

Gnomad ASJ exome

AF:

0.0303

Gnomad EAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.0647

Gnomad NFE exome

AF:

0.0647

Gnomad OTH exome

AF:

0.0590

GnomAD4 exome

AF:

0.0772

AC:

112089

AN:

1452666

Hom.:

5059

Cov.:

AF XY:

0.0791

AC XY:

57214

AN XY:

723320

show subpopulations

African (AFR)

AF:

0.0881

AC:

2316

AN:

26302

American (AMR)

AF:

0.0313

AC:

1384

AN:

44188

Ashkenazi Jewish (ASJ)

AF:

0.0348

AC:

910

AN:

26134

East Asian (EAS)

AF:

0.221

AC:

8774

AN:

39700

South Asian (SAS)

AF:

0.133

AC:

11498

AN:

86204

European-Finnish (FIN)

AF:

0.0699

AC:

3731

AN:

53396

Middle Eastern (MID)

AF:

0.0582

AC:

332

AN:

5702

European-Non Finnish (NFE)

AF:

0.0710

AC:

78922

AN:

1111518

Other (OTH)

AF:

0.0709

AC:

4222

AN:

59522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

6269

12537

18806

25074

31343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3080

6160

9240

12320

15400

<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:

0.0784

AC:

11028

AN:

140726

Hom.:

495

Cov.:

AF XY:

0.0808

AC XY:

5565

AN XY:

68862

show subpopulations

African (AFR)

AF:

0.0875

AC:

2852

AN:

32606

American (AMR)

AF:

0.0477

AC:

689

AN:

14436

Ashkenazi Jewish (ASJ)

AF:

0.0346

AC:

120

AN:

3466

East Asian (EAS)

AF:

0.211

AC:

1092

AN:

5174

South Asian (SAS)

AF:

0.139

AC:

660

AN:

4762

European-Finnish (FIN)

AF:

0.0691

AC:

707

AN:

10232

Middle Eastern (MID)

AF:

0.0669

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0706

AC:

4724

AN:

66896

Other (OTH)

AF:

0.0504

AC:

100

AN:

1984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

519

1038

1557

2076

2595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0694

Hom.:

Bravo

AF:

0.0684

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

Mar 26, 2012

Leiden Muscular Dystrophy (MYL2)

Significance:not provided

Review Status:no classification provided

Collection Method:curation

Jun 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Primary familial hypertrophic cardiomyopathy

Benign:1

Apr 28, 2015

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.23

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over