NM_033118.4:c.193A>T

Variant names:

• chr20-31820266-A-T
• NM_033118.4:c.193A>T
• MYLK2 p.Thr65Ser

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.193A>T​(p.Thr65Ser) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T65I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYLK2 NM_033118.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.586
• Publications: 0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=0.066963136).

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.193A>T	p.Thr65Ser	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.193A>T	p.Thr65Ser	missense	Exon 3 of 13	ENSP00000365152.4	Q9H1R3
	MYLK2	ENST00000375994.6	TSL:1	c.193A>T	p.Thr65Ser	missense	Exon 2 of 12	ENSP00000365162.2	Q9H1R3
	MYLK2	ENST00000965978.1		c.193A>T	p.Thr65Ser	missense	Exon 3 of 13	ENSP00000636037.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.6
DANN	Benign	0.39
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.59
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.043
Sift	Benign	0.12	T
Sift4G	Benign	0.45	T
Varity_R		0.029
gMVP		0.025

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-30408069;