Genetic Variant MYL2:c.169+671T>G (chr12-110915044-A-C) – 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.169+671T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,162 control chromosomes in the GnomAD database, including 42,897 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.74 ( 42897 hom., cov: 32)

Consequence

MYL2
NM_000432.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.37

Publications

11 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: Labcorp Genetics (formerly Invitae), G2P
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:

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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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000432.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYL2	NM_000432.4	MANE Select	c.169+671T>G	intron	N/A	NP_000423.2	P10916
MYL2	NM_001406745.1		c.94-720T>G	intron	N/A	NP_001393674.1	G3V1V8
MYL2	NM_001406916.1		c.112+671T>G	intron	N/A	NP_001393845.1	A0A590UJU8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYL2	ENST00000228841.15	TSL:1 MANE Select	c.169+671T>G	intron	N/A	ENSP00000228841.8	P10916
MYL2	ENST00000713800.1		c.169+671T>G	intron	N/A	ENSP00000519106.1	P10916
MYL2	ENST00000713803.1		c.169+671T>G	intron	N/A	ENSP00000519109.1	P10916

Frequencies

GnomAD3 genomes

AF:

0.743

AC:

113006

AN:

152044

Hom.:

42846

Cov.:

show subpopulations

Gnomad AFR

AF:

0.893

Gnomad AMI

AF:

0.777

Gnomad AMR

AF:

0.745

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.680

Gnomad SAS

AF:

0.718

Gnomad FIN

AF:

0.677

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.679

Gnomad OTH

AF:

0.708

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.743

AC:

113126

AN:

152162

Hom.:

42897

Cov.:

AF XY:

0.742

AC XY:

55197

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.893

AC:

37099

AN:

41526

American (AMR)

AF:

0.745

AC:

11389

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.551

AC:

1909

AN:

3466

East Asian (EAS)

AF:

0.680

AC:

3522

AN:

5176

South Asian (SAS)

AF:

0.719

AC:

3468

AN:

4822

European-Finnish (FIN)

AF:

0.677

AC:

7156

AN:

10568

Middle Eastern (MID)

AF:

0.731

AC:

215

AN:

294

European-Non Finnish (NFE)

AF:

0.679

AC:

46174

AN:

68008

Other (OTH)

AF:

0.705

AC:

1487

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1409

2818

4228

5637

7046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

840

1680

2520

3360

4200

<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:

0.690

Hom.:

72643

Bravo

AF:

0.752

Asia WGS

AF:

0.695

AC:

2415

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.21

(source)

DANN

Benign

0.71

PhyloP100

-2.4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over