dbSNP rs2071629: MYL2:c.275-58G>A (chr12-110913382-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000432.4(MYL2):c.275-58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 1,586,164 control chromosomes in the GnomAD database, including 5,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.072 ( 497 hom., cov: 33)

Exomes 𝑓: 0.077 ( 5007 hom. )

Consequence

MYL2
NM_000432.4 intron

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.0630

Publications

14 publications found

Variant links:

Genes affected

MYL2 (HGNC:7583): (myosin light chain 2) This gene encodes a major sarcomeric protein in mammalian striated muscle. The encoded protein plays a role in embryonic heart muscle structure and function, while phosphorylation of the encoded protein is involved in cardiac myosin cycling kinetics, torsion and function in adults. Mutations in this gene are associated with hypertrophic cardiomyopathy 10 and infant-onset myopathy. [provided by RefSeq, May 2022]

MYL2 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 10
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
congenital fiber-type disproportion myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MYL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYL2	NM_000432.4 link	c.275-58G>A	intron_variant	Intron 4 of 6	ENST00000228841.15	NP_000423.2	P10916Q6IB42
MYL2	NM_001406745.1 link	c.233-58G>A	intron_variant	Intron 3 of 5		NP_001393674.1
MYL2	NM_001406916.1 link	c.218-58G>A	intron_variant	Intron 4 of 6		NP_001393845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL2	ENST00000228841.15 link	c.275-58G>A		intron_variant	Intron 4 of 6	1	NM_000432.4	ENSP00000228841.8		P10916

Frequencies

GnomAD3 genomes

AF:

0.0725

AC:

11032

AN:

152106

Hom.:

498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0686

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0451

Gnomad ASJ

AF:

0.0346

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.0664

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0695

Gnomad OTH

AF:

0.0485

GnomAD4 exome

AF:

0.0769

AC:

110203

AN:

1433940

Hom.:

5007

AF XY:

0.0789

AC XY:

56404

AN XY:

714928

show subpopulations

African (AFR)

AF:

0.0689

AC:

2264

AN:

32854

American (AMR)

AF:

0.0310

AC:

1379

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.0347

AC:

901

AN:

25976

East Asian (EAS)

AF:

0.221

AC:

8736

AN:

39544

South Asian (SAS)

AF:

0.133

AC:

11419

AN:

85572

European-Finnish (FIN)

AF:

0.0698

AC:

3725

AN:

53364

Middle Eastern (MID)

AF:

0.0575

AC:

328

AN:

5706

European-Non Finnish (NFE)

AF:

0.0711

AC:

77306

AN:

1086950

Other (OTH)

AF:

0.0697

AC:

4145

AN:

59444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

5689

11379

17068

22758

28447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2992

5984

8976

11968

14960

<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:

0.0725

AC:

11033

AN:

152224

Hom.:

497

Cov.:

AF XY:

0.0748

AC XY:

5564

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0687

AC:

2853

AN:

41546

American (AMR)

AF:

0.0450

AC:

688

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0346

AC:

120

AN:

3470

East Asian (EAS)

AF:

0.212

AC:

1093

AN:

5164

South Asian (SAS)

AF:

0.137

AC:

661

AN:

4826

European-Finnish (FIN)

AF:

0.0664

AC:

704

AN:

10604

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0696

AC:

4730

AN:

68004

Other (OTH)

AF:

0.0475

AC:

100

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

516

1031

1547

2062

2578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0728

Hom.:

614

Bravo

AF:

0.0685

Asia WGS

AF:

0.111

AC:

385

AN:

3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

Leiden Muscular Dystrophy (MYL2)

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.6

(source)

DANN

Benign

0.82

PhyloP100

0.063

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over