rs374233822

Variant names:

• chr20-31832016-C-G
• rs374233822
• NM_033118.4:c.1590C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-31832016-C-G
• chr20-31832016-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033118.4(MYLK2):​c.1590C>G​(p.Asn530Lys) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N530N) 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: -0.0280
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26438782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK2	NM_033118.4	c.1590C>G	p.Asn530Lys	missense_variant	Exon 12 of 13	ENST00000375985.5	NP_149109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK2	ENST00000375985.5	c.1590C>G	p.Asn530Lys	missense_variant	Exon 12 of 13	1	NM_033118.4	ENSP00000365152.4
MYLK2	ENST00000375994.6	c.1590C>G	p.Asn530Lys	missense_variant	Exon 11 of 12	1		ENSP00000365162.2
MYLK2	ENST00000468730.1	n.528C>G		non_coding_transcript_exon_variant	Exon 5 of 6	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 240260 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.72	.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.89	L;L
PhyloP100		-0.028
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.056
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		0.0080	B;B
Vest4		0.33
MutPred		0.67		Gain of MoRF binding (P = 0.0206);Gain of MoRF binding (P = 0.0206);
MVP		0.47
MPC		0.15
ClinPred		0.61	D
GERP RS		0.51
Varity_R		0.29
gMVP		0.54
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs374233822; hg19: chr20-30419819;