Variant 20-31826818-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_033118.4(MYLK2):c.1104C>T(p.Phe368=) 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:4

Conservation

PhyloP100: 0.247

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=-0.31).

BP6

Variant 20-31826818-C-T is Benign according to our data. Variant chr20-31826818-C-T is described in ClinVar as [Benign]. Clinvar id is 46518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-31826818-C-T is described in Lovd as [Benign]. Variant chr20-31826818-C-T is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2642 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLK2	NM_033118.4 linkuse as main transcript	c.1104C>T	p.Phe368=	synonymous_variant	8/13	ENST00000375985.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MYLK2	ENST00000375985.5 linkuse as main transcript	c.1104C>T	p.Phe368=	synonymous_variant	8/13	1	NM_033118.4	P1
MYLK2	ENST00000375994.6 linkuse as main transcript	c.1104C>T	p.Phe368=	synonymous_variant	7/12	1		P1
MYLK2	ENST00000468730.1 linkuse as main transcript	n.42C>T		non_coding_transcript_exon_variant	1/6	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

GnomAD3 exomes

AF:

0.0207

AC:

5206

AN:

251280

Hom.:

AF XY:

0.0203

AC XY:

2759

AN XY:

135818

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 SAS exome

AF:

0.0112

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

Gnomad4 AFR exome

AF:

0.00341

Gnomad4 AMR exome

AF:

0.0304

Gnomad4 ASJ exome

AF:

0.00329

Gnomad4 EAS exome

AF:

0.000479

Gnomad4 SAS exome

AF:

0.0110

Gnomad4 FIN exome

AF:

0.0327

Gnomad4 NFE exome

AF:

0.0264

Gnomad4 OTH exome

AF:

0.0189

GnomAD4 genome

AF:

0.0174

AC:

2642

AN:

152166

Hom.:

Cov.:

AF XY:

0.0175

AC XY:

1300

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00489

Gnomad4 AMR

AF:

0.0190

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00770

Gnomad4 FIN

AF:

0.0347

Gnomad4 NFE

AF:

0.0249

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0205

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 25, 2012	2.2% (155/7020) of Eur Amer chrom in ESP -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 09, 2013	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

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

9.4

DANN

Benign

0.73

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

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