chr20-31821517-C-A

Position:

• chr20-31821517-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033118.4(MYLK2):​c.552C>A​(p.Ser184Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYLK2 NM_033118.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.133

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053082645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYLK2	NM_033118.4	c.552C>A	p.Ser184Arg	missense_variant	4/13	ENST00000375985.5	NP_149109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYLK2	ENST00000375985.5	c.552C>A	p.Ser184Arg	missense_variant	4/13	1	NM_033118.4	ENSP00000365152	P1
MYLK2	ENST00000375994.6	c.552C>A	p.Ser184Arg	missense_variant	3/12	1		ENSP00000365162	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461680 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Jun 24, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.9
DANN	Benign	0.63
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.33	.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.41	N;N
REVEL	Benign	0.042
Sift	Uncertain	0.0080	D;D
Sift4G	Benign	0.35	T;T
Polyphen		0.20	B;B
Vest4		0.14
MutPred		0.13		Loss of phosphorylation at S184 (P = 0.0169);Loss of phosphorylation at S184 (P = 0.0169);
MVP		0.50
MPC		0.096
ClinPred		0.13	T
GERP RS		-1.1
Varity_R		0.096
gMVP		0.20

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: rs786205284; hg19: chr20-30409320;