chr20-31824298-C-T

Position:

chr20-31824298-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id is 36654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-31824298-C-T is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1770 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYLK2	NM_033118.4 linkuse as main transcript	c.918C>T	p.Ala306Ala	synonymous_variant	6/13	ENST00000375985.5	NP_149109.1	Q9H1R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYLK2	ENST00000375985.5 linkuse as main transcript	c.918C>T	p.Ala306Ala	synonymous_variant	6/13	1	NM_033118.4	ENSP00000365152.4		Q9H1R3
MYLK2	ENST00000375994.6 linkuse as main transcript	c.918C>T	p.Ala306Ala	synonymous_variant	5/12	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

GnomAD3 exomes

AF:

0.0107

AC:

2665

AN:

249978

Hom.:

AF XY:

0.0111

AC XY:

1504

AN XY:

135340

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 SAS exome

AF:

0.00802

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

Gnomad4 AFR exome

AF:

0.00370

Gnomad4 AMR exome

AF:

0.00837

Gnomad4 ASJ exome

AF:

0.00165

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00830

Gnomad4 FIN exome

AF:

0.00384

Gnomad4 NFE exome

AF:

0.0207

Gnomad4 OTH exome

AF:

0.0142

GnomAD4 genome

AF:

0.0116

AC:

1770

AN:

152280

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

831

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00361

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00725

Gnomad4 FIN

AF:

0.00255

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.0189

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 10, 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, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 10, 2012	- -

Hypertrophic cardiomyopathy 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 11, 2023	- -

Cardiomyopathy

Benign:1

Benign, no assertion criteria provided

clinical testing

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

Jun 04, 2015

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.65

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