20-31819317-AC-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000375994.6(MYLK2):c.-260del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 527,948 control chromosomes in the GnomAD database, including 26 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (18 hom.)
• Consequence: MYLK2 ENST00000375994.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.63

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 20-31819317-AC-A is Benign according to our data. Variant chr20-31819317-AC-A is described in ClinVar as [Likely_benign]. Clinvar id is 1191659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 778 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLK2	NM_033118.4			upstream_gene_variant		ENST00000375985.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLK2	ENST00000375994.6	c.-260del		5_prime_UTR_variant	1/12	1		P1
MYLK2	ENST00000375985.5			upstream_gene_variant		1	NM_033118.4	P1

Frequencies

GnomAD3 genomes AF: 0.00514 AC: 778 AN: 151342 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.000827

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00270

Gnomad ASJ AF: 0.00405

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00315

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00754

Gnomad OTH AF: 0.00145

GnomAD4 exome AF: 0.00593 AC: 2232 AN: 376490 Hom.: 18 Cov.: 1 AF XY: 0.00585 AC XY: 1177 AN XY: 201180

Gnomad4 AFR exome AF: 0.000539

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.00214

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00410

Gnomad4 FIN exome AF: 0.0163

Gnomad4 NFE exome AF: 0.00692

Gnomad4 OTH exome AF: 0.00530

GnomAD4 genome AF: 0.00514 AC: 779 AN: 151458 Hom.: 8 Cov.: 32 AF XY: 0.00554 AC XY: 410 AN XY: 73994

Gnomad4 AFR AF: 0.000824

Gnomad4 AMR AF: 0.00269

Gnomad4 ASJ AF: 0.00405

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00315

Gnomad4 FIN AF: 0.0151

Gnomad4 NFE AF: 0.00755

Gnomad4 OTH AF: 0.00144

Alfa AF: 0.00664 Hom.: 0

Bravo AF: 0.00361

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 24, 2019

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Computational scores

Source: dbNSFP v4.3

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: rs556265822; hg19: chr20-30407120;