20-31832151-A-G

Variant names:

• chr20-31832151-A-G
• rs6060980
• NM_033118.4:c.1710+15A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000375985.5(MYLK2):​c.1710+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 963,036 control chromosomes in the GnomAD database, including 4,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (661 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3827 hom.)
• Consequence: MYLK2 ENST00000375985.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0320
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-31832151-A-G is Benign according to our data. Variant chr20-31832151-A-G is described in ClinVar as Benign. ClinVar VariationId is 36651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375985.5. 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.1710+15A>G		intron	N/A	NP_149109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK2	ENST00000375985.5	TSL:1 MANE Select	c.1710+15A>G		intron	N/A	ENSP00000365152.4
	MYLK2	ENST00000375994.6	TSL:1	c.1710+15A>G		intron	N/A	ENSP00000365162.2
	MYLK2	ENST00000468730.1	TSL:1	n.648+15A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0915 AC: 13207 AN: 144404 Hom.: 657 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.0869

Gnomad EAS AF: 0.00119

Gnomad SAS AF: 0.0327

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0769

Gnomad OTH AF: 0.0975

GnomAD2 exomes AF: 0.0634 AC: 14802 AN: 233616 AF XY: 0.0615

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.0449

Gnomad ASJ exome AF: 0.0818

Gnomad EAS exome AF: 0.000169

Gnomad FIN exome AF: 0.0709

Gnomad NFE exome AF: 0.0751

Gnomad OTH exome AF: 0.0716

GnomAD4 exome AF: 0.121 AC: 99100 AN: 818470 Hom.: 3827 Cov.: 26 AF XY: 0.114 AC XY: 48318 AN XY: 423708

African (AFR) AF: 0.212 AC: 4729 AN: 22310

American (AMR) AF: 0.0523 AC: 2035 AN: 38936

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 2127 AN: 18298

East Asian (EAS) AF: 0.000178 AC: 4 AN: 22428

South Asian (SAS) AF: 0.0320 AC: 2276 AN: 71170

European-Finnish (FIN) AF: 0.0911 AC: 3520 AN: 38646

Middle Eastern (MID) AF: 0.180 AC: 777 AN: 4324

European-Non Finnish (NFE) AF: 0.140 AC: 79318 AN: 567576

Other (OTH) AF: 0.124 AC: 4314 AN: 34782

GnomAD4 genome AF: 0.0916 AC: 13245 AN: 144566 Hom.: 661 Cov.: 32 AF XY: 0.0895 AC XY: 6299 AN XY: 70418

African (AFR) AF: 0.143 AC: 5809 AN: 40528

American (AMR) AF: 0.0622 AC: 914 AN: 14704

Ashkenazi Jewish (ASJ) AF: 0.0869 AC: 291 AN: 3348

East Asian (EAS) AF: 0.00119 AC: 5 AN: 4202

South Asian (SAS) AF: 0.0331 AC: 133 AN: 4020

European-Finnish (FIN) AF: 0.0834 AC: 768 AN: 9210

Middle Eastern (MID) AF: 0.113 AC: 32 AN: 284

European-Non Finnish (NFE) AF: 0.0769 AC: 5028 AN: 65346

Other (OTH) AF: 0.0970 AC: 199 AN: 2052

Alfa AF: 0.0789 Hom.: 1697

Bravo AF: 0.0895

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0010
DANN	Benign	0.29
PhyloP100		-0.032
Mutation Taster		=100/0	polymorphism (auto)

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: rs6060980; hg19: chr20-30419954;