20-31820417-A-G

Variant names:

• chr20-31820417-A-G
• NM_033118.4:c.344A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_033118.4(MYLK2):​c.344A>G​(p.Gln115Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: MYLK2 NM_033118.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.972

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12950894).
• BS2: High AC in GnomAdExome4 at 5 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK2	NM_033118.4	c.344A>G	p.Gln115Arg	missense_variant	Exon 3 of 13	ENST00000375985.5	NP_149109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK2	ENST00000375985.5	c.344A>G	p.Gln115Arg	missense_variant	Exon 3 of 13	1	NM_033118.4	ENSP00000365152.4
MYLK2	ENST00000375994.6	c.344A>G	p.Gln115Arg	missense_variant	Exon 2 of 12	1		ENSP00000365162.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460574 Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 4 AN XY: 726592

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.7
DANN	Benign	0.82
DEOGEN2	Benign	0.27	T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.30	.;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.83	N;N
REVEL	Benign	0.090
Sift	Uncertain	0.019	D;D
Sift4G	Benign	0.51	T;T
Polyphen		0.22	B;B
Vest4		0.38
MutPred		0.19		Gain of MoRF binding (P = 0.0148);Gain of MoRF binding (P = 0.0148);
MVP		0.72
MPC		0.11
ClinPred		0.14	T
GERP RS		4.7
Varity_R		0.063
gMVP		0.043

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-30408220;