20-31824298-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_033118.4(MYLK2):c.918C>T(p.Ala306Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,613,686 control chromosomes in the GnomAD database, including 319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 21 hom., cov: 33)

Exomes 𝑓: 0.017 ( 298 hom. )

Consequence

MYLK2
NM_033118.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.839

Publications

7 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

MYLK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 20-31824298-C-T is Benign according to our data. Variant chr20-31824298-C-T is described in ClinVar as Benign. ClinVar VariationId is 36654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.839 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0116 (1770/152280) while in subpopulation NFE AF = 0.0186 (1267/68020). AF 95% confidence interval is 0.0178. There are 21 homozygotes in GnomAd4. There are 831 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1770 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK2	NM_033118.4 link	c.918C>T	p.Ala306Ala	synonymous_variant	Exon 6 of 13	ENST00000375985.5	NP_149109.1	Q9H1R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK2	ENST00000375985.5 link	c.918C>T	p.Ala306Ala	synonymous_variant	Exon 6 of 13	1	NM_033118.4	ENSP00000365152.4		Q9H1R3
MYLK2	ENST00000375994.6 link	c.918C>T	p.Ala306Ala	synonymous_variant	Exon 5 of 12	1		ENSP00000365162.2		Q9H1R3

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1771

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00745

Gnomad FIN

AF:

0.00255

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0191

GnomAD2 exomes

AF:

0.0107

AC:

2665

AN:

249978

AF XY:

0.0111

show subpopulations

Gnomad AFR exome

AF:

0.00366

Gnomad AMR exome

AF:

0.00750

Gnomad ASJ exome

AF:

0.00239

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00242

Gnomad NFE exome

AF:

0.0171

Gnomad OTH exome

AF:

0.0151

GnomAD4 exome

AF:

0.0174

AC:

25356

AN:

1461406

Hom.:

298

Cov.:

AF XY:

0.0170

AC XY:

12370

AN XY:

726964

show subpopulations

African (AFR)

AF:

0.00370

AC:

124

AN:

33476

American (AMR)

AF:

0.00837

AC:

374

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00165

AC:

AN:

26124

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39696

South Asian (SAS)

AF:

0.00830

AC:

715

AN:

86130

European-Finnish (FIN)

AF:

0.00384

AC:

205

AN:

53346

Middle Eastern (MID)

AF:

0.00780

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0207

AC:

22988

AN:

1111810

Other (OTH)

AF:

0.0142

AC:

859

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

1527

3055

4582

6110

7637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.0116

AC:

1770

AN:

152280

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

831

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00361

AC:

150

AN:

41564

American (AMR)

AF:

0.0150

AC:

229

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.00725

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00255

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0186

AC:

1267

AN:

68020

Other (OTH)

AF:

0.0189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

190

285

380

475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0126

Hom.:

Bravo

AF:

0.0118

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0184

EpiControl

AF:

0.0169

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 10, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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. -

Apr 10, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypertrophic cardiomyopathy 1

Benign:2

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 11, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiomyopathy

Benign:1

Jun 04, 2015

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

0.84

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over