rs28763880

Variant names:

• chr20-31820175-A-G
• rs28763880
• NM_033118.4:c.102A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_033118.4(MYLK2):​c.102A>G​(p.Lys34Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,614,032 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (12 hom.)
• Consequence: MYLK2 NM_033118.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.122
• Publications: 3 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 20-31820175-A-G is Benign according to our data. Variant chr20-31820175-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.122 with no splicing effect.
• BS2: High AC in GnomAd4 at 159 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK2	NM_033118.4	MANE Select	c.102A>G	p.Lys34Lys	synonymous	Exon 3 of 13	NP_149109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK2	ENST00000375985.5	TSL:1 MANE Select	c.102A>G	p.Lys34Lys	synonymous	Exon 3 of 13	ENSP00000365152.4
	MYLK2	ENST00000375994.6	TSL:1	c.102A>G	p.Lys34Lys	synonymous	Exon 2 of 12	ENSP00000365162.2

Frequencies

GnomAD3 genomes AF: 0.00105 AC: 160 AN: 152204 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00102 AC: 255 AN: 250470 AF XY: 0.00117

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00172 AC: 2518 AN: 1461710 Hom.: 12 Cov.: 32 AF XY: 0.00175 AC XY: 1276 AN XY: 727148

African (AFR) AF: 0.000239 AC: 8 AN: 33480

American (AMR) AF: 0.000715 AC: 32 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00246 AC: 212 AN: 86258

European-Finnish (FIN) AF: 0.0000751 AC: 4 AN: 53246

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.00188 AC: 2096 AN: 1112006

Other (OTH) AF: 0.00270 AC: 163 AN: 60394

GnomAD4 genome AF: 0.00104 AC: 159 AN: 152322 Hom.: 1 Cov.: 32 AF XY: 0.00101 AC XY: 75 AN XY: 74482

African (AFR) AF: 0.000241 AC: 10 AN: 41570

American (AMR) AF: 0.00183 AC: 28 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00157 AC: 107 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000935 Hom.: 0

Bravo AF: 0.00104

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00234

EpiControl AF: 0.000948

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Cardiomyopathy (1)
-	-	1	Hypertrophic cardiomyopathy 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		-0.12
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: rs28763880; hg19: chr20-30407978; COSMIC: COSV65658957;