rs146497334

Positions:

chr20-31833784-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_033118.4(MYLK2):c.1778C>T(p.Ala593Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000738 in 1,613,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

MYLK2
NM_033118.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 5.59

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:

MYLK2 (HGNC:):

MYLK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024363667).

BP6

Variant 20-31833784-C-T is Benign according to our data. Variant chr20-31833784-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 413772.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1, Benign=1}. Variant chr20-31833784-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 72 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYLK2	NM_033118.4 linkuse as main transcript	c.1778C>T	p.Ala593Val	missense_variant	13/13	ENST00000375985.5	NP_149109.1	Q9H1R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYLK2	ENST00000375985.5 linkuse as main transcript	c.1778C>T	p.Ala593Val	missense_variant	13/13	1	NM_033118.4	ENSP00000365152.4	Q9H1R3
MYLK2	ENST00000375994.6 linkuse as main transcript	c.1778C>T	p.Ala593Val	missense_variant	12/12	1		ENSP00000365162.2	Q9H1R3
MYLK2	ENST00000468730.1 linkuse as main transcript	n.716C>T		non_coding_transcript_exon_variant	6/6	1

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000920

AC:

AN:

250112

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1460728

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000473

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000487

Hom.:

Bravo

AF:

0.000434

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hypertrophic cardiomyopathy 1

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	Jun 06, 2022	ACMG classification criteria: BP4 supporting -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 30, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 15, 2020

The p.Ala593Val variant in MYLK2 is classified as benign because it has been identified in 0.16% (41/24934) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

T;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.80

.;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

0.69

N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.61

P;P

Vest4

0.17

MVP

0.71

MPC

0.26

ClinPred

0.15

GERP RS

5.0

Varity_R

0.21

gMVP

0.63

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.

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