rs76530988

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_033118.4(MYLK2):c.1082+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 1,614,012 control chromosomes in the GnomAD database, including 608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 42 hom., cov: 31)

Exomes 𝑓: 0.025 ( 566 hom. )

Consequence

MYLK2
NM_033118.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.02

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 20-31826725-G-A is Benign according to our data. Variant chr20-31826725-G-A is described in ClinVar as [Benign]. Clinvar id is 36649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-31826725-G-A is described in Lovd as [Benign]. Variant chr20-31826725-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0192 (2923/152168) while in subpopulation NFE AF= 0.0278 (1890/67988). AF 95% confidence interval is 0.0268. There are 42 homozygotes in gnomad4. There are 1432 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2923 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK2	NM_033118.4 link	c.1082+11G>A		intron_variant	Intron 7 of 12	ENST00000375985.5	NP_149109.1	Q9H1R3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYLK2	ENST00000375985.5 link	c.1082+11G>A	intron_variant	Intron 7 of 12	1	NM_033118.4	ENSP00000365152.4	Q9H1R3
MYLK2	ENST00000375994.6 link	c.1082+11G>A	intron_variant	Intron 6 of 11	1		ENSP00000365162.2	Q9H1R3
MYLK2	ENST00000468730.1 link	n.-52G>A	upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0192

AC:

2926

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00483

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0180

Gnomad ASJ

AF:

0.0361

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.0367

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0278

Gnomad OTH

AF:

0.0168

GnomAD3 exomes

AF:

0.0203

AC:

5105

AN:

251324

Hom.:

AF XY:

0.0205

AC XY:

2782

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00499

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.0372

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00186

Gnomad FIN exome

AF:

0.0397

Gnomad NFE exome

AF:

0.0282

Gnomad OTH exome

AF:

0.0227

GnomAD4 exome

AF:

0.0250

AC:

36576

AN:

1461844

Hom.:

566

Cov.:

AF XY:

0.0244

AC XY:

17719

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00436

Gnomad4 AMR exome

AF:

0.0125

Gnomad4 ASJ exome

AF:

0.0347

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00185

Gnomad4 FIN exome

AF:

0.0393

Gnomad4 NFE exome

AF:

0.0281

Gnomad4 OTH exome

AF:

0.0225

GnomAD4 genome

AF:

0.0192

AC:

2923

AN:

152168

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

1432

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00479

Gnomad4 AMR

AF:

0.0179

Gnomad4 ASJ

AF:

0.0361

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.0367

Gnomad4 NFE

AF:

0.0278

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0220

Hom.:

Bravo

AF:

0.0178

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 24, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Sep 27, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cardiomyopathy

Benign:1

Aug 18, 2011

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Hypertrophic cardiomyopathy 1

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.51

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