20-31824298-C-T

Variant names:

• chr20-31824298-C-T
• rs41293106
• NM_033118.4:c.918C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_033118.4(MYLK2):​c.918C>T​(p.Ala306Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,613,686 control chromosomes in the GnomAD database, including 319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (21 hom., cov: 33)
  • Exomes 𝑓: 0.017 (298 hom.)
• Consequence: MYLK2 NM_033118.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.839
• Publications: 7 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 20-31824298-C-T is Benign according to our data. Variant chr20-31824298-C-T is described in ClinVar as Benign. ClinVar VariationId is 36654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.839 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0116 (1770/152280) while in subpopulation NFE AF = 0.0186 (1267/68020). AF 95% confidence interval is 0.0178. There are 21 homozygotes in GnomAd4. There are 831 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1770 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033118.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK2	NM_033118.4	MANE Select	c.918C>T	p.Ala306Ala	synonymous	Exon 6 of 13	NP_149109.1	Q9H1R3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK2	ENST00000375985.5	TSL:1 MANE Select	c.918C>T	p.Ala306Ala	synonymous	Exon 6 of 13	ENSP00000365152.4	Q9H1R3
	MYLK2	ENST00000375994.6	TSL:1	c.918C>T	p.Ala306Ala	synonymous	Exon 5 of 12	ENSP00000365162.2	Q9H1R3
	MYLK2	ENST00000965978.1		c.918C>T	p.Ala306Ala	synonymous	Exon 6 of 13	ENSP00000636037.1

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1771 AN: 152162 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.00362

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00745

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.0191

GnomAD2 exomes AF: 0.0107 AC: 2665 AN: 249978 AF XY: 0.0111

Gnomad AFR exome AF: 0.00366

Gnomad AMR exome AF: 0.00750

Gnomad ASJ exome AF: 0.00239

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00242

Gnomad NFE exome AF: 0.0171

Gnomad OTH exome AF: 0.0151

GnomAD4 exome AF: 0.0174 AC: 25356 AN: 1461406 Hom.: 298 Cov.: 33 AF XY: 0.0170 AC XY: 12370 AN XY: 726964

African (AFR) AF: 0.00370 AC: 124 AN: 33476

American (AMR) AF: 0.00837 AC: 374 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00165 AC: 43 AN: 26124

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39696

South Asian (SAS) AF: 0.00830 AC: 715 AN: 86130

European-Finnish (FIN) AF: 0.00384 AC: 205 AN: 53346

Middle Eastern (MID) AF: 0.00780 AC: 45 AN: 5766

European-Non Finnish (NFE) AF: 0.0207 AC: 22988 AN: 1111810

Other (OTH) AF: 0.0142 AC: 859 AN: 60380

GnomAD4 genome AF: 0.0116 AC: 1770 AN: 152280 Hom.: 21 Cov.: 33 AF XY: 0.0112 AC XY: 831 AN XY: 74460

African (AFR) AF: 0.00361 AC: 150 AN: 41564

American (AMR) AF: 0.0150 AC: 229 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00725 AC: 35 AN: 4828

European-Finnish (FIN) AF: 0.00255 AC: 27 AN: 10602

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0186 AC: 1267 AN: 68020

Other (OTH) AF: 0.0189 AC: 40 AN: 2114

Alfa AF: 0.0126 Hom.: 8

Bravo AF: 0.0118

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0184

EpiControl AF: 0.0169

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Hypertrophic cardiomyopathy 1 (2)
-	-	1	Cardiomyopathy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.65
PhyloP100		0.84
Mutation Taster		=100/0	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: rs41293106; hg19: chr20-30412101;