rs2233260

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -0.211
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]

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 id is 31774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-110913195-G-A is described in Lovd as [Benign].
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
MYL2NM_000432.4 linkc.353+51C>T intron_variant Intron 5 of 6 ENST00000228841.15 NP_000423.2 P10916Q6IB42
MYL2NM_001406745.1 linkc.311+51C>T intron_variant Intron 4 of 5 NP_001393674.1
MYL2NM_001406916.1 linkc.296+51C>T intron_variant Intron 5 of 6 NP_001393845.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYL2ENST00000228841.15 linkc.353+51C>T intron_variant Intron 5 of 6 1 NM_000432.4 ENSP00000228841.8 P10916

Frequencies

GnomAD3 genomes
AF:
0.212
AC:
32017
AN:
151328
Hom.:
3690
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.158
Gnomad AMI
AF:
0.320
Gnomad AMR
AF:
0.279
Gnomad ASJ
AF:
0.110
Gnomad EAS
AF:
0.00423
Gnomad SAS
AF:
0.111
Gnomad FIN
AF:
0.275
Gnomad MID
AF:
0.199
Gnomad NFE
AF:
0.245
Gnomad OTH
AF:
0.213
GnomAD2 exomes
AF:
0.210
AC:
52206
AN:
248922
AF XY:
0.205
show subpopulations
Gnomad AFR exome
AF:
0.158
Gnomad AMR exome
AF:
0.324
Gnomad ASJ exome
AF:
0.113
Gnomad EAS exome
AF:
0.00273
Gnomad FIN exome
AF:
0.265
Gnomad NFE exome
AF:
0.234
Gnomad OTH exome
AF:
0.220
GnomAD4 exome
AF:
0.232
AC:
338628
AN:
1461718
Hom.:
42096
Cov.:
38
AF XY:
0.227
AC XY:
164966
AN XY:
727160
show subpopulations
African (AFR)
AF:
0.147
AC:
4929
AN:
33480
American (AMR)
AF:
0.322
AC:
14397
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
0.118
AC:
3079
AN:
26134
East Asian (EAS)
AF:
0.00194
AC:
77
AN:
39700
South Asian (SAS)
AF:
0.126
AC:
10842
AN:
86246
European-Finnish (FIN)
AF:
0.265
AC:
14151
AN:
53420
Middle Eastern (MID)
AF:
0.156
AC:
902
AN:
5768
European-Non Finnish (NFE)
AF:
0.249
AC:
277000
AN:
1111862
Other (OTH)
AF:
0.219
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
AF:
0.211
AC:
32023
AN:
151448
Hom.:
3694
Cov.:
33
AF XY:
0.210
AC XY:
15570
AN XY:
74050
show subpopulations
African (AFR)
AF:
0.158
AC:
6428
AN:
40788
American (AMR)
AF:
0.279
AC:
4268
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.110
AC:
380
AN:
3464
East Asian (EAS)
AF:
0.00444
AC:
23
AN:
5186
South Asian (SAS)
AF:
0.111
AC:
534
AN:
4824
European-Finnish (FIN)
AF:
0.275
AC:
2911
AN:
10592
Middle Eastern (MID)
AF:
0.211
AC:
62
AN:
294
European-Non Finnish (NFE)
AF:
0.245
AC:
16681
AN:
67992
Other (OTH)
AF:
0.211
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
70-75
75-80
>80
Age
Alfa
AF:
0.230
Hom.:
3556
Bravo
AF:
0.214

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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.61
DANN
Benign
0.56
PhyloP100
-0.21
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2233260; hg19: chr12-111350999; COSMIC: COSV57406861; API