rs76530988

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000375985.5(MYLK2):​c.1082+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 1,614,012 control chromosomes in the GnomAD database, including 608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 42 hom., cov: 31)
Exomes 𝑓: 0.025 ( 566 hom. )

Consequence

MYLK2
ENST00000375985.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.02
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 20-31826725-G-A is Benign according to our data. Variant chr20-31826725-G-A is described in ClinVar as [Benign]. Clinvar id is 36649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-31826725-G-A is described in Lovd as [Benign]. Variant chr20-31826725-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0192 (2923/152168) while in subpopulation NFE AF= 0.0278 (1890/67988). AF 95% confidence interval is 0.0268. There are 42 homozygotes in gnomad4. There are 1432 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2923 AD,Digenic gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYLK2NM_033118.4 linkuse as main transcriptc.1082+11G>A intron_variant ENST00000375985.5 NP_149109.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYLK2ENST00000375985.5 linkuse as main transcriptc.1082+11G>A intron_variant 1 NM_033118.4 ENSP00000365152 P1
MYLK2ENST00000375994.6 linkuse as main transcriptc.1082+11G>A intron_variant 1 ENSP00000365162 P1

Frequencies

GnomAD3 genomes
AF:
0.0192
AC:
2926
AN:
152050
Hom.:
42
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00483
Gnomad AMI
AF:
0.00220
Gnomad AMR
AF:
0.0180
Gnomad ASJ
AF:
0.0361
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000416
Gnomad FIN
AF:
0.0367
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.0278
Gnomad OTH
AF:
0.0168
GnomAD3 exomes
AF:
0.0203
AC:
5105
AN:
251324
Hom.:
92
AF XY:
0.0205
AC XY:
2782
AN XY:
135856
show subpopulations
Gnomad AFR exome
AF:
0.00499
Gnomad AMR exome
AF:
0.0113
Gnomad ASJ exome
AF:
0.0372
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00186
Gnomad FIN exome
AF:
0.0397
Gnomad NFE exome
AF:
0.0282
Gnomad OTH exome
AF:
0.0227
GnomAD4 exome
AF:
0.0250
AC:
36576
AN:
1461844
Hom.:
566
Cov.:
33
AF XY:
0.0244
AC XY:
17719
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.00436
Gnomad4 AMR exome
AF:
0.0125
Gnomad4 ASJ exome
AF:
0.0347
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00185
Gnomad4 FIN exome
AF:
0.0393
Gnomad4 NFE exome
AF:
0.0281
Gnomad4 OTH exome
AF:
0.0225
GnomAD4 genome
AF:
0.0192
AC:
2923
AN:
152168
Hom.:
42
Cov.:
31
AF XY:
0.0192
AC XY:
1432
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.00479
Gnomad4 AMR
AF:
0.0179
Gnomad4 ASJ
AF:
0.0361
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000416
Gnomad4 FIN
AF:
0.0367
Gnomad4 NFE
AF:
0.0278
Gnomad4 OTH
AF:
0.0166
Alfa
AF:
0.0220
Hom.:
14
Bravo
AF:
0.0178
Asia WGS
AF:
0.00202
AC:
8
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Benign, criteria provided, single submitterclinical testingGeneDxJan 24, 2014This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineSep 27, 2011- -
not provided Benign:2
Likely benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Cardiomyopathy Benign:1
Benign, criteria provided, single submittercurationWomen's Health and Genetics/Laboratory Corporation of America, LabCorpAug 18, 2011- -
Hypertrophic cardiomyopathy 1 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
10
DANN
Benign
0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs76530988; hg19: chr20-30414528; API