Variant rs6058469 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000375985.5(MYLK2):c.684T>C(p.Ile228=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 1,613,856 control chromosomes in the GnomAD database, including 4,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 663 hom., cov: 33)

Exomes 𝑓: 0.072 ( 4147 hom. )

Consequence

MYLK2
ENST00000375985.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0970

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 20-31821649-T-C is Benign according to our data. Variant chr20-31821649-T-C is described in ClinVar as [Benign]. Clinvar id is 46528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-31821649-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.097 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYLK2	NM_033118.4 linkuse as main transcript	c.684T>C	p.Ile228=	synonymous_variant	4/13	ENST00000375985.5	NP_149109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYLK2	ENST00000375985.5 linkuse as main transcript	c.684T>C	p.Ile228=	synonymous_variant	4/13	1	NM_033118.4	ENSP00000365152	P1
MYLK2	ENST00000375994.6 linkuse as main transcript	c.684T>C	p.Ile228=	synonymous_variant	3/12	1		ENSP00000365162	P1

Frequencies

GnomAD3 genomes

AF:

0.0877

AC:

13327

AN:

152012

Hom.:

659

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.0624

Gnomad ASJ

AF:

0.0856

Gnomad EAS

AF:

0.000967

Gnomad SAS

AF:

0.0268

Gnomad FIN

AF:

0.0725

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0766

Gnomad OTH

AF:

0.0957

GnomAD3 exomes

AF:

0.0653

AC:

16412

AN:

251312

Hom.:

696

AF XY:

0.0636

AC XY:

8638

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.0459

Gnomad ASJ exome

AF:

0.0826

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0256

Gnomad FIN exome

AF:

0.0705

Gnomad NFE exome

AF:

0.0785

Gnomad OTH exome

AF:

0.0742

GnomAD4 exome

AF:

0.0716

AC:

104602

AN:

1461726

Hom.:

4147

Cov.:

AF XY:

0.0702

AC XY:

51073

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.140

Gnomad4 AMR exome

AF:

0.0485

Gnomad4 ASJ exome

AF:

0.0860

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0266

Gnomad4 FIN exome

AF:

0.0701

Gnomad4 NFE exome

AF:

0.0757

Gnomad4 OTH exome

AF:

0.0754

GnomAD4 genome

AF:

0.0878

AC:

13364

AN:

152130

Hom.:

663

Cov.:

AF XY:

0.0852

AC XY:

6338

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.0622

Gnomad4 ASJ

AF:

0.0856

Gnomad4 EAS

AF:

0.000969

Gnomad4 SAS

AF:

0.0272

Gnomad4 FIN

AF:

0.0725

Gnomad4 NFE

AF:

0.0767

Gnomad4 OTH

AF:

0.0952

Alfa

AF:

0.0814

Hom.:

375

Bravo

AF:

0.0903

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0881

EpiControl

AF:

0.0847

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 15, 2014	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Dec 14, 2011	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hypertrophic cardiomyopathy 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over