rs2233260
Variant names: 
Your query was ambiguous. Multiple possible variants found: 
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000432.4(MYL2):c.353+51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,613,166 control chromosomes in the GnomAD database, including 45,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
 Genomes: 𝑓 0.21   (  3694   hom.,  cov: 33) 
 Exomes 𝑓:  0.23   (  42096   hom.  ) 
Consequence
 MYL2
NM_000432.4 intron
NM_000432.4 intron
Scores
 2
Clinical Significance
Conservation
 PhyloP100:  -0.211  
Publications
8 publications found 
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 cardiomyopathyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- hypertrophic cardiomyopathy 10Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
- myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathyInheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
- congenital fiber-type disproportion myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- dilated cardiomyopathyInheritance: AD Classification: LIMITED Submitted by: ClinGen
- arrhythmogenic right ventricular cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85). 
BP6
Variant 12-110913195-G-A is Benign according to our data. Variant chr12-110913195-G-A is described in ClinVar as Benign. ClinVar VariationId is 31774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. 
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272  is higher than 0.05. 
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt | 
|---|---|---|---|---|---|---|---|---|
| MYL2 | NM_000432.4 | c.353+51C>T | intron_variant | Intron 5 of 6 | ENST00000228841.15 | NP_000423.2 | ||
| MYL2 | NM_001406745.1 | c.311+51C>T | intron_variant | Intron 4 of 5 | NP_001393674.1 | |||
| MYL2 | NM_001406916.1 | c.296+51C>T | intron_variant | Intron 5 of 6 | NP_001393845.1 | 
Ensembl
Frequencies
GnomAD3 genomes  0.212  AC: 32017AN: 151328Hom.:  3690  Cov.: 33 show subpopulations 
GnomAD3 genomes 
 AF: 
AC: 
32017
AN: 
151328
Hom.: 
Cov.: 
33
Gnomad AFR 
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Gnomad AMI 
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Gnomad AMR 
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Gnomad SAS 
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Gnomad FIN 
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Gnomad MID 
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Gnomad NFE 
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Gnomad OTH 
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GnomAD2 exomes  AF:  0.210  AC: 52206AN: 248922 AF XY:  0.205   show subpopulations 
GnomAD2 exomes 
 AF: 
AC: 
52206
AN: 
248922
 AF XY: 
Gnomad AFR exome 
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Gnomad AMR exome 
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Gnomad ASJ exome 
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Gnomad EAS exome 
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Gnomad FIN exome 
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Gnomad NFE exome 
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Gnomad OTH exome 
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GnomAD4 exome  AF:  0.232  AC: 338628AN: 1461718Hom.:  42096  Cov.: 38 AF XY:  0.227  AC XY: 164966AN XY: 727160 show subpopulations 
GnomAD4 exome 
 AF: 
AC: 
338628
AN: 
1461718
Hom.: 
Cov.: 
38
 AF XY: 
AC XY: 
164966
AN XY: 
727160
show subpopulations 
African (AFR) 
 AF: 
AC: 
4929
AN: 
33480
American (AMR) 
 AF: 
AC: 
14397
AN: 
44714
Ashkenazi Jewish (ASJ) 
 AF: 
AC: 
3079
AN: 
26134
East Asian (EAS) 
 AF: 
AC: 
77
AN: 
39700
South Asian (SAS) 
 AF: 
AC: 
10842
AN: 
86246
European-Finnish (FIN) 
 AF: 
AC: 
14151
AN: 
53420
Middle Eastern (MID) 
 AF: 
AC: 
902
AN: 
5768
European-Non Finnish (NFE) 
 AF: 
AC: 
277000
AN: 
1111862
Other (OTH) 
 AF: 
AC: 
13251
AN: 
60394
 Allele Balance Distribution 
 Red line indicates average allele balance 
 Average allele balance: 0.494 
Heterozygous variant carriers
 0 
 16200 
 32400 
 48600 
 64800 
 81000 
 0.00 
 0.20 
 0.40 
 0.60 
 0.80 
 0.95 
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
 0 
 9288 
 18576 
 27864 
 37152 
 46440 
 <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  0.211  AC: 32023AN: 151448Hom.:  3694  Cov.: 33 AF XY:  0.210  AC XY: 15570AN XY: 74050 show subpopulations 
GnomAD4 genome 
 AF: 
AC: 
32023
AN: 
151448
Hom.: 
Cov.: 
33
 AF XY: 
AC XY: 
15570
AN XY: 
74050
show subpopulations 
African (AFR) 
 AF: 
AC: 
6428
AN: 
40788
American (AMR) 
 AF: 
AC: 
4268
AN: 
15286
Ashkenazi Jewish (ASJ) 
 AF: 
AC: 
380
AN: 
3464
East Asian (EAS) 
 AF: 
AC: 
23
AN: 
5186
South Asian (SAS) 
 AF: 
AC: 
534
AN: 
4824
European-Finnish (FIN) 
 AF: 
AC: 
2911
AN: 
10592
Middle Eastern (MID) 
 AF: 
AC: 
62
AN: 
294
European-Non Finnish (NFE) 
 AF: 
AC: 
16681
AN: 
67992
Other (OTH) 
 AF: 
AC: 
445
AN: 
2112
 Allele Balance Distribution 
 Red line indicates average allele balance 
 Average allele balance: 0.497 
Heterozygous variant carriers
 0 
 1295 
 2590 
 3884 
 5179 
 6474 
 0.00 
 0.20 
 0.40 
 0.60 
 0.80 
 0.95 
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
 0 
 320 
 640 
 960 
 1280 
 1600 
 <30 
 30-35 
 35-40 
 40-45 
 45-50 
 50-55 
 55-60 
 60-65 
 65-70 
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 >80 
Age
Alfa 
 AF: 
Hom.: 
Bravo 
 AF: 
ClinVar
Significance: Benign 
Submissions summary: Benign:2Other:1 
Revision: criteria provided, multiple submitters, no conflicts
LINK: link 
Submissions by phenotype
not provided    Benign:2Other:1 
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Mar 26, 2012
Leiden Muscular Dystrophy (MYL2)
Significance:not provided
Review Status:no classification provided
Collection Method:curation
- -
Mar 03, 2015
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source: 
Name
Calibrated prediction
Score
Prediction
 BayesDel_noAF 
 Benign 
 DANN 
 Benign 
 PhyloP100 
Splicing
Name
Calibrated prediction
Score
Prediction
 SpliceAI score (max) 
Details are displayed if max score is > 0.2
 Find out detailed SpliceAI scores and Pangolin per-transcript scores at 
Publications
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