20-31826818-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.1104C>T(p.Phe368Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 1,614,006 control chromosomes in the GnomAD database, including 543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 35 hom., cov: 31)

Exomes 𝑓: 0.024 ( 508 hom. )

Consequence

MYLK2
NM_033118.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.247

Publications

6 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=-0.31).

BP6

Variant 20-31826818-C-T is Benign according to our data. Variant chr20-31826818-C-T is described in ClinVar as Benign. ClinVar VariationId is 46518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.247 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0174 (2642/152166) while in subpopulation NFE AF = 0.0249 (1692/68004). AF 95% confidence interval is 0.0239. There are 35 homozygotes in GnomAd4. There are 1300 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 2642 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK2	NM_033118.4 link	c.1104C>T	p.Phe368Phe	synonymous_variant	Exon 8 of 13	ENST00000375985.5	NP_149109.1	Q9H1R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYLK2	ENST00000375985.5 link	c.1104C>T	p.Phe368Phe	synonymous_variant	Exon 8 of 13	1	NM_033118.4	ENSP00000365152.4	Q9H1R3
MYLK2	ENST00000375994.6 link	c.1104C>T	p.Phe368Phe	synonymous_variant	Exon 7 of 12	1		ENSP00000365162.2	Q9H1R3
MYLK2	ENST00000468730.1 link	n.42C>T		non_coding_transcript_exon_variant	Exon 1 of 6	1

Frequencies

GnomAD3 genomes

AF:

0.0174

AC:

2645

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00491

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0191

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.00790

Gnomad FIN

AF:

0.0347

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0249

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.0207

AC:

5206

AN:

251280

AF XY:

0.0203

show subpopulations

Gnomad AFR exome

AF:

0.00357

Gnomad AMR exome

AF:

0.0340

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.000435

Gnomad FIN exome

AF:

0.0332

Gnomad NFE exome

AF:

0.0242

Gnomad OTH exome

AF:

0.0196

GnomAD4 exome

AF:

0.0238

AC:

34837

AN:

1461840

Hom.:

508

Cov.:

AF XY:

0.0234

AC XY:

17043

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.00341

AC:

114

AN:

33480

American (AMR)

AF:

0.0304

AC:

1358

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00329

AC:

AN:

26136

East Asian (EAS)

AF:

0.000479

AC:

AN:

39698

South Asian (SAS)

AF:

0.0110

AC:

953

AN:

86248

European-Finnish (FIN)

AF:

0.0327

AC:

1747

AN:

53418

Middle Eastern (MID)

AF:

0.00832

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0264

AC:

29369

AN:

1111992

Other (OTH)

AF:

0.0189

AC:

1143

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

2266

4532

6799

9065

11331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1116

2232

3348

4464

5580

<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:

0.0174

AC:

2642

AN:

152166

Hom.:

Cov.:

AF XY:

0.0175

AC XY:

1300

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00489

AC:

203

AN:

41500

American (AMR)

AF:

0.0190

AC:

291

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3470

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.00770

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.0347

AC:

368

AN:

10600

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0249

AC:

1692

AN:

68004

Other (OTH)

AF:

0.0109

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

137

274

412

549

686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0224

Hom.:

Bravo

AF:

0.0152

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0225

EpiControl

AF:

0.0221

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

May 25, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

2.2% (155/7020) of Eur Amer chrom in ESP -

Dec 09, 2013

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. -

Hypertrophic cardiomyopathy 1

Benign:2

Nov 22, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

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

-0.31

CADD

Benign

9.4

(source)

DANN

Benign

0.73

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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