rs17340555

Variant names:

• chr20-31834775-T-C
• rs17340555
• NM_033118.4:c.*978T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033118.4(MYLK2):​c.*978T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 152,794 control chromosomes in the GnomAD database, including 504 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.069 (503 hom., cov: 33)
  • Exomes 𝑓: 0.12 (1 hom.)
• Consequence: MYLK2 NM_033118.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.88
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.098 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK2	NM_033118.4	c.*978T>C		downstream_gene_variant		ENST00000375985.5	NP_149109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK2	ENST00000375985.5	c.*978T>C		downstream_gene_variant		1	NM_033118.4	ENSP00000365152.4
MYLK2	ENST00000375994.6	c.*978T>C		downstream_gene_variant		1		ENSP00000365162.2
MYLK2	ENST00000468730.1	n.*86T>C		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0687 AC: 10464 AN: 152224 Hom.: 503 Cov.: 33

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0587

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0598

GnomAD4 exome AF: 0.124 AC: 56 AN: 452 Hom.: 1 AF XY: 0.109 AC XY: 30 AN XY: 274

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.121 AC: 52 AN: 428

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.222 AC: 4 AN: 18

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0687 AC: 10461 AN: 152342 Hom.: 503 Cov.: 33 AF XY: 0.0696 AC XY: 5184 AN XY: 74498

African (AFR) AF: 0.0171 AC: 713 AN: 41576

American (AMR) AF: 0.0585 AC: 896 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 271 AN: 3472

East Asian (EAS) AF: 0.000770 AC: 4 AN: 5192

South Asian (SAS) AF: 0.0207 AC: 100 AN: 4834

European-Finnish (FIN) AF: 0.143 AC: 1519 AN: 10622

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6802 AN: 68020

Other (OTH) AF: 0.0591 AC: 125 AN: 2114

Alfa AF: 0.0864 Hom.: 1193

Bravo AF: 0.0609

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.098
DANN	Benign	0.20
PhyloP100		-2.9
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs17340555; hg19: chr20-30422578;