dbSNP rs113936360: MYLK2:c.1295+4C>A (chr20-31830893-C-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_033118.4(MYLK2):c.1295+4C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000332 in 1,613,680 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

MYLK2
NM_033118.4 splice_region, intron

Scores

Splicing: ADA: 0.00005731

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.435

Publications

2 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 20-31830893-C-A is Benign according to our data. Variant chr20-31830893-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 252 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.1295+4C>A		splice_region 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.1295+4C>A	splice_region intron	N/A	ENSP00000365152.4	Q9H1R3
MYLK2	ENST00000375994.6	TSL:1	c.1295+4C>A	splice_region intron	N/A	ENSP00000365162.2	Q9H1R3
MYLK2	ENST00000468730.1	TSL:1	n.233+4C>A	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00163

AC:

247

AN:

151762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00581

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000418

AC:

105

AN:

251154

AF XY:

0.000280

show subpopulations

Gnomad AFR exome

AF:

0.00597

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000194

AC:

284

AN:

1461800

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

127

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.00636

AC:

213

AN:

33474

American (AMR)

AF:

0.000246

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111946

Other (OTH)

AF:

0.000878

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00166

AC:

252

AN:

151880

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

123

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.00592

AC:

245

AN:

41408

American (AMR)

AF:

0.000458

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67906

Other (OTH)

AF:

0.00

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00136

Hom.:

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hypertrophic cardiomyopathy 1 (4)

not specified (3)

not provided (2)

Cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

0.43

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000057

dbscSNV1_RF

Benign

0.17

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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