rs1060500984

Variant names:

• chr20-31820129-A-G
• rs1060500984
• NM_033118.4:c.56A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033118.4(MYLK2):​c.56A>G​(p.Lys19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYLK2 NM_033118.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.680
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy 1

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057002544).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033118.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK2	NM_033118.4	MANE Select	c.56A>G	p.Lys19Arg	missense	Exon 3 of 13	NP_149109.1	Q9H1R3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK2	ENST00000375985.5	TSL:1 MANE Select	c.56A>G	p.Lys19Arg	missense	Exon 3 of 13	ENSP00000365152.4	Q9H1R3
	MYLK2	ENST00000375994.6	TSL:1	c.56A>G	p.Lys19Arg	missense	Exon 2 of 12	ENSP00000365162.2	Q9H1R3
	MYLK2	ENST00000965978.1		c.56A>G	p.Lys19Arg	missense	Exon 3 of 13	ENSP00000636037.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Hypertrophic cardiomyopathy 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.68
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.047
Sift	Benign	0.033	D
Sift4G	Benign	0.45	T
Polyphen		0.020	B
Vest4		0.17
MutPred		0.13		Loss of ubiquitination at K19 (P = 8e-04)
MVP		0.51
MPC		0.071
ClinPred		0.080	T
GERP RS		2.3
Varity_R		0.066
gMVP		0.030
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1060500984; hg19: chr20-30407932;