chr12-110913195-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000432.4(MYL2):c.353+51C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,613,286 control chromosomes in the GnomAD database, including 231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 14 hom., cov: 33)

Exomes 𝑓: 0.014 ( 217 hom. )

Consequence

MYL2
NM_000432.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.211

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 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=-0.85).

BP6

Variant 12-110913195-G-T is Benign according to our data. Variant chr12-110913195-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 671321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-110913195-G-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0122 (1848/151498) while in subpopulation NFE AF = 0.0153 (1041/68008). AF 95% confidence interval is 0.0145. There are 14 homozygotes in GnomAd4. There are 1002 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYL2	NM_000432.4 link	c.353+51C>A	intron_variant	Intron 5 of 6	ENST00000228841.15	NP_000423.2	P10916Q6IB42
MYL2	NM_001406745.1 link	c.311+51C>A	intron_variant	Intron 4 of 5		NP_001393674.1
MYL2	NM_001406916.1 link	c.296+51C>A	intron_variant	Intron 5 of 6		NP_001393845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL2	ENST00000228841.15 link	c.353+51C>A		intron_variant	Intron 5 of 6	1	NM_000432.4	ENSP00000228841.8		P10916

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1847

AN:

151378

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00209

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00600

Gnomad FIN

AF:

0.0457

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0153

Gnomad OTH

AF:

0.00957

GnomAD2 exomes

AF:

0.0136

AC:

3387

AN:

248922

AF XY:

0.0138

show subpopulations

Gnomad AFR exome

AF:

0.00171

Gnomad AMR exome

AF:

0.00770

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.000114

Gnomad FIN exome

AF:

0.0486

Gnomad NFE exome

AF:

0.0154

Gnomad OTH exome

AF:

0.0160

GnomAD4 exome

AF:

0.0143

AC:

20939

AN:

1461788

Hom.:

217

Cov.:

AF XY:

0.0141

AC XY:

10278

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.00179

AC:

AN:

33480

American (AMR)

AF:

0.00803

AC:

359

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00210

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00630

AC:

543

AN:

86250

European-Finnish (FIN)

AF:

0.0429

AC:

2291

AN:

53420

Middle Eastern (MID)

AF:

0.00555

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0152

AC:

16923

AN:

1111928

Other (OTH)

AF:

0.0111

AC:

673

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1342

2683

4025

5366

6708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0122

AC:

1848

AN:

151498

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1002

AN XY:

74082

show subpopulations

African (AFR)

AF:

0.00208

AC:

AN:

40806

American (AMR)

AF:

0.0114

AC:

175

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3464

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0457

AC:

484

AN:

10596

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0153

AC:

1041

AN:

68008

Other (OTH)

AF:

0.00947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

177

266

354

443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00151

Hom.:

3556

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.48

(source)

DANN

Benign

0.65

PhyloP100

-0.21

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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chr12-110913195-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over