20-31819896-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033118.4(MYLK2):c.53-230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0876 in 152,246 control chromosomes in the GnomAD database, including 660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.088 (660 hom., cov: 32)
• Consequence: MYLK2 NM_033118.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.03

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 20-31819896-G-A is Benign according to our data. Variant chr20-31819896-G-A is described in ClinVar as [Benign]. Clinvar id is 678612.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLK2	NM_033118.4	c.53-230G>A		intron_variant		ENST00000375985.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLK2	ENST00000375985.5	c.53-230G>A		intron_variant		1	NM_033118.4	P1
MYLK2	ENST00000375994.6	c.53-230G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0874 AC: 13299 AN: 152128 Hom.: 657 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0622

Gnomad ASJ AF: 0.0856

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0265

Gnomad FIN AF: 0.0727

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0953

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0876 AC: 13335 AN: 152246 Hom.: 660 Cov.: 32 AF XY: 0.0848 AC XY: 6316 AN XY: 74448

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.0621

Gnomad4 ASJ AF: 0.0856

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0269

Gnomad4 FIN AF: 0.0727

Gnomad4 NFE AF: 0.0766

Gnomad4 OTH AF: 0.0948

Alfa AF: 0.0815 Hom.: 90

Bravo AF: 0.0902

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.17
Dann	Benign	0.55

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: rs1009454; hg19: chr20-30407699;