chr20-31821588-G-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_033118.4(MYLK2):​c.623G>A​(p.Gly208Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G208R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MYLK2
NM_033118.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.272

Publications

0 publications found
Variant links:
Genes affected
MYLK2 (HGNC:16243): (myosin light chain kinase 2) This gene encodes a myosin light chain kinase, a calcium/calmodulin dependent enzyme, that is exclusively expressed in adult skeletal muscle. [provided by RefSeq, Jul 2008]
MYLK2 Gene-Disease associations (from GenCC):
  • hypertrophic cardiomyopathy 1
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • hypertrophic cardiomyopathy
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07639176).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYLK2NM_033118.4 linkc.623G>A p.Gly208Glu missense_variant Exon 4 of 13 ENST00000375985.5 NP_149109.1 Q9H1R3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYLK2ENST00000375985.5 linkc.623G>A p.Gly208Glu missense_variant Exon 4 of 13 1 NM_033118.4 ENSP00000365152.4 Q9H1R3
MYLK2ENST00000375994.6 linkc.623G>A p.Gly208Glu missense_variant Exon 3 of 12 1 ENSP00000365162.2 Q9H1R3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461756
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
727178
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.0000580
AC:
5
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53290
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1112008
Other (OTH)
AF:
0.00
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Jun 24, 2013
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
15
DANN
Benign
0.93
DEOGEN2
Benign
0.19
T;T
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.61
.;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.076
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.63
N;N
PhyloP100
0.27
PrimateAI
Benign
0.28
T
PROVEAN
Benign
0.25
N;N
REVEL
Benign
0.041
Sift
Benign
0.20
T;T
Sift4G
Benign
0.57
T;T
Polyphen
0.0090
B;B
Vest4
0.11
MutPred
0.18
Loss of methylation at K205 (P = 0.0779);Loss of methylation at K205 (P = 0.0779);
MVP
0.58
MPC
0.12
ClinPred
0.072
T
GERP RS
0.12
Varity_R
0.062
gMVP
0.19
Mutation Taster
=94/6
polymorphism

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: rs786205407; hg19: chr20-30409391; API