Genetic Variant MYLK2:c.*978T>C (chr20-31834775-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033118.4(MYLK2):c.*978T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 152,794 control chromosomes in the GnomAD database, including 504 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.069 ( 503 hom., cov: 33)

Exomes 𝑓: 0.12 ( 1 hom. )

Consequence

MYLK2
NM_033118.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.88

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.098 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033118.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK2	NM_033118.4	MANE Select	c.*978T>C		downstream_gene	N/A	NP_149109.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYLK2	ENST00000375985.5	TSL:1 MANE Select	c.*978T>C	downstream_gene	N/A	ENSP00000365152.4
MYLK2	ENST00000375994.6	TSL:1	c.*978T>C	downstream_gene	N/A	ENSP00000365162.2
MYLK2	ENST00000468730.1	TSL:1	n.*86T>C	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0687

AC:

10464

AN:

152224

Hom.:

503

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0172

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0587

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.143

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.0598

GnomAD4 exome

AF:

0.124

AC:

AN:

452

Hom.:

AF XY:

0.109

AC XY:

AN XY:

274

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.121

AC:

AN:

428

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.222

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0687

AC:

10461

AN:

152342

Hom.:

503

Cov.:

AF XY:

0.0696

AC XY:

5184

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0171

AC:

713

AN:

41576

American (AMR)

AF:

0.0585

AC:

896

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0781

AC:

271

AN:

3472

East Asian (EAS)

AF:

0.000770

AC:

AN:

5192

South Asian (SAS)

AF:

0.0207

AC:

100

AN:

4834

European-Finnish (FIN)

AF:

0.143

AC:

1519

AN:

10622

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.100

AC:

6802

AN:

68020

Other (OTH)

AF:

0.0591

AC:

125

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

491

982

1474

1965

2456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0864

Hom.:

1193

Bravo

AF:

0.0609

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.098

(source)

DANN

Benign

0.20

PhyloP100

-2.9

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over