chr20-31826818-C-T

Position:

• chr20-31826818-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_033118.4(MYLK2):​c.1104C>T​(p.Phe368=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 1,614,006 control chromosomes in the GnomAD database, including 543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (35 hom., cov: 31)
  • Exomes 𝑓: 0.024 (508 hom.)
• Consequence: MYLK2 NM_033118.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.247

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 Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 20-31826818-C-T is Benign according to our data. Variant chr20-31826818-C-T is described in ClinVar as [Benign]. Clinvar id is 46518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-31826818-C-T is described in Lovd as [Benign]. Variant chr20-31826818-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.247 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0174 (2642/152166) while in subpopulation NFE AF= 0.0249 (1692/68004). AF 95% confidence interval is 0.0239. There are 35 homozygotes in gnomad4. There are 1300 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2642 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYLK2	NM_033118.4	c.1104C>T	p.Phe368=	synonymous_variant	8/13	ENST00000375985.5	NP_149109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYLK2	ENST00000375985.5	c.1104C>T	p.Phe368=	synonymous_variant	8/13	1	NM_033118.4	ENSP00000365152	P1
MYLK2	ENST00000375994.6	c.1104C>T	p.Phe368=	synonymous_variant	7/12	1		ENSP00000365162	P1
MYLK2	ENST00000468730.1	n.42C>T		non_coding_transcript_exon_variant	1/6	1

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2645 AN: 152048 Hom.: 35 Cov.: 31

Gnomad AFR AF: 0.00491

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.00790

Gnomad FIN AF: 0.0347

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0249

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.0207 AC: 5206 AN: 251280 Hom.: 82 AF XY: 0.0203 AC XY: 2759 AN XY: 135818

Gnomad AFR exome AF: 0.00357

Gnomad AMR exome AF: 0.0340

Gnomad ASJ exome AF: 0.00298

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.0112

Gnomad FIN exome AF: 0.0332

Gnomad NFE exome AF: 0.0242

Gnomad OTH exome AF: 0.0196

GnomAD4 exome AF: 0.0238 AC: 34837 AN: 1461840 Hom.: 508 Cov.: 33 AF XY: 0.0234 AC XY: 17043 AN XY: 727218

Gnomad4 AFR exome AF: 0.00341

Gnomad4 AMR exome AF: 0.0304

Gnomad4 ASJ exome AF: 0.00329

Gnomad4 EAS exome AF: 0.000479

Gnomad4 SAS exome AF: 0.0110

Gnomad4 FIN exome AF: 0.0327

Gnomad4 NFE exome AF: 0.0264

Gnomad4 OTH exome AF: 0.0189

GnomAD4 genome AF: 0.0174 AC: 2642 AN: 152166 Hom.: 35 Cov.: 31 AF XY: 0.0175 AC XY: 1300 AN XY: 74396

Gnomad4 AFR AF: 0.00489

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.00770

Gnomad4 FIN AF: 0.0347

Gnomad4 NFE AF: 0.0249

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0205 Hom.: 18

Bravo AF: 0.0152

Asia WGS AF: 0.00462 AC: 17 AN: 3478

EpiCase AF: 0.0225

EpiControl AF: 0.0221

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 09, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 25, 2012	2.2% (155/7020) of Eur Amer chrom in ESP -

Hypertrophic cardiomyopathy 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.4
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs6089088; hg19: chr20-30414621;