Genetic Variant NM_033118.4:c.1710+15A>G (chr20-31832151-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033118.4(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
NM_033118.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0320

Publications

8 publications found

Variant links:

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

MYLK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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: 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.1710+15A>G		intron	N/A	NP_149109.1	Q9H1R3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYLK2	ENST00000375985.5	TSL:1 MANE Select	c.1710+15A>G	intron	N/A	ENSP00000365152.4	Q9H1R3
MYLK2	ENST00000375994.6	TSL:1	c.1710+15A>G	intron	N/A	ENSP00000365162.2	Q9H1R3
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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.114

AC XY:

48318

AN XY:

423708

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

4080

8160

12240

16320

20400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2934

5868

8802

11736

14670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0916

AC:

13245

AN:

144566

Hom.:

661

Cov.:

AF XY:

0.0895

AC XY:

6299

AN XY:

70418

show subpopulations

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:

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:

AN:

284

European-Non Finnish (NFE)

AF:

0.0769

AC:

5028

AN:

65346

Other (OTH)

AF:

0.0970

AC:

199

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

599

1198

1796

2395

2994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0789

Hom.:

1697

Bravo

AF:

0.0895

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Cardiomyopathy (1)

Hypertrophic cardiomyopathy 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

(source)

DANN

Benign

0.29

PhyloP100

-0.032

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over