20-31819630-C-G

Variant names:

• chr20-31819630-C-G
• NM_033118.4:c.50C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033118.4(MYLK2):​c.50C>G​(p.Thr17Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: MYLK2 NM_033118.4 missense, splice_region
• Scores: Splicing: ADA: 0.9857
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK2	NM_033118.4	c.50C>G	p.Thr17Arg	missense_variant, splice_region_variant	Exon 2 of 13	ENST00000375985.5	NP_149109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK2	ENST00000375985.5	c.50C>G	p.Thr17Arg	missense_variant, splice_region_variant	Exon 2 of 13	1	NM_033118.4	ENSP00000365152.4
MYLK2	ENST00000375994.6	c.50C>G	p.Thr17Arg	missense_variant, splice_region_variant	Exon 1 of 12	1		ENSP00000365162.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399264 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690114

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.0086	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;T
Eigen	Benign	0.063
Eigen_PC	Benign	0.072
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.55	.;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.57	N;N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.74	P;P
Vest4		0.28
MutPred		0.14		Loss of phosphorylation at T17 (P = 0.0108);Loss of phosphorylation at T17 (P = 0.0108);
MVP		0.74
MPC		0.38
ClinPred		0.82	D
GERP RS		3.5
Varity_R		0.21
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.75
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-30407433;