Genetic Variant MYLK2:c.1710+15A>G (chr20-31832151-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033118.4(MYLK2):c.1710+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 963,036 control chromosomes in the GnomAD database, including 4,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 661 hom., cov: 32)

Exomes 𝑓: 0.12 ( 3827 hom. )

Consequence

MYLK2
NM_033118.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0320

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=-0.91).

BP6

Variant 20-31832151-A-G is Benign according to our data. Variant chr20-31832151-A-G is described in ClinVar as [Benign]. Clinvar id is 36651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-31832151-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK2	NM_033118.4 link	c.1710+15A>G		intron_variant	Intron 12 of 12	ENST00000375985.5	NP_149109.1	Q9H1R3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYLK2	ENST00000375985.5 link	c.1710+15A>G	intron_variant	Intron 12 of 12	1	NM_033118.4	ENSP00000365152.4	Q9H1R3
MYLK2	ENST00000375994.6 link	c.1710+15A>G	intron_variant	Intron 11 of 11	1		ENSP00000365162.2	Q9H1R3
MYLK2	ENST00000468730.1 link	n.648+15A>G	intron_variant	Intron 5 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.0915

AC:

13207

AN:

144404

Hom.:

657

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0623

Gnomad ASJ

AF:

0.0869

Gnomad EAS

AF:

0.00119

Gnomad SAS

AF:

0.0327

Gnomad FIN

AF:

0.0834

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0769

Gnomad OTH

AF:

0.0975

GnomAD3 exomes

AF:

0.0634

AC:

14802

AN:

233616

Hom.:

587

AF XY:

0.0615

AC XY:

7755

AN XY:

126086

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.0449

Gnomad ASJ exome

AF:

0.0818

Gnomad EAS exome

AF:

0.000169

Gnomad SAS exome

AF:

0.0262

Gnomad FIN exome

AF:

0.0709

Gnomad NFE exome

AF:

0.0751

Gnomad OTH exome

AF:

0.0716

GnomAD4 exome

AF:

0.121

AC:

99100

AN:

818470

Hom.:

3827

Cov.:

AF XY:

0.114

AC XY:

48318

AN XY:

423708

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.0523

Gnomad4 ASJ exome

AF:

0.116

Gnomad4 EAS exome

AF:

0.000178

Gnomad4 SAS exome

AF:

0.0320

Gnomad4 FIN exome

AF:

0.0911

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.0916

AC:

13245

AN:

144566

Hom.:

661

Cov.:

AF XY:

0.0895

AC XY:

6299

AN XY:

70418

show subpopulations

Gnomad4 AFR

AF:

0.143

Gnomad4 AMR

AF:

0.0622

Gnomad4 ASJ

AF:

0.0869

Gnomad4 EAS

AF:

0.00119

Gnomad4 SAS

AF:

0.0331

Gnomad4 FIN

AF:

0.0834

Gnomad4 NFE

AF:

0.0769

Gnomad4 OTH

AF:

0.0970

Alfa

AF:

0.0763

Hom.:

956

Bravo

AF:

0.0895

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 15, 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. -

Apr 19, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.91

CADD

Benign

0.0010

DANN

Benign

0.29

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