rs76530988

Positions:

• chr20-31826725-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.02

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]

ACMG classification

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/exons	MANE	Protein	UniProt
MYLK2	NM_033118.4	c.1082+11G>A		intron_variant		ENST00000375985.5	NP_149109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYLK2	ENST00000375985.5	c.1082+11G>A		intron_variant		1	NM_033118.4	ENSP00000365152.4
MYLK2	ENST00000375994.6	c.1082+11G>A		intron_variant		1		ENSP00000365162.2

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2926 AN: 152050 Hom.: 42 Cov.: 31

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.: 92 AF XY: 0.0205 AC XY: 2782 AN XY: 135856

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.: 33 AF XY: 0.0244 AC XY: 17719 AN XY: 727216

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.: 42 Cov.: 31 AF XY: 0.0192 AC XY: 1432 AN XY: 74404

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.: 14

Bravo AF: 0.0178

Asia WGS AF: 0.00202 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Sep 27, 2011	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 24, 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. -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Cardiomyopathy Benign:1

Benign, criteria provided, single submitter

curation

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

Aug 18, 2011

- -

Hypertrophic cardiomyopathy 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
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

Other links and lift over

dbSNP: rs76530988; hg19: chr20-30414528;