Variant 12-110914159-GACAC-GACACAC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000432.4(MYL2):c.274+26_274+27insGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 1,369,570 control chromosomes in the GnomAD database, including 1,729 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 549 hom., cov: 31)

Exomes 𝑓: 0.076 ( 1180 hom. )

Consequence

MYL2
NM_000432.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.360

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 12-110914159-G-GAC is Benign according to our data. Variant chr12-110914159-G-GAC is described in ClinVar as [Likely_benign]. Clinvar id is 43462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
MYL2	NM_000432.4 linkuse as main transcript	c.274+26_274+27insGT	intron_variant	ENST00000228841.15
MYL2	NM_001406745.1 linkuse as main transcript	c.232+26_232+27insGT	intron_variant
MYL2	NM_001406916.1 linkuse as main transcript	c.217+26_217+27insGT	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
MYL2	ENST00000228841.15 linkuse as main transcript	c.274+26_274+27insGT	intron_variant	1	NM_000432.4	P1
MYL2	ENST00000548438.1 linkuse as main transcript	c.232+26_232+27insGT	intron_variant	3
MYL2	ENST00000663220.1 linkuse as main transcript	c.217+26_217+27insGT	intron_variant
MYL2	ENST00000549029.1 linkuse as main transcript	n.105+26_105+27insGT	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0776

AC:

11644

AN:

149990

Hom.:

550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0819

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0457

Gnomad ASJ

AF:

0.0351

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.0682

Gnomad MID

AF:

0.0649

Gnomad NFE

AF:

0.0702

Gnomad OTH

AF:

0.0533

GnomAD4 exome

AF:

0.0764

AC:

93138

AN:

1219476

Hom.:

1180

Cov.:

AF XY:

0.0794

AC XY:

48757

AN XY:

613876

show subpopulations

Gnomad4 AFR exome

AF:

0.0809

Gnomad4 AMR exome

AF:

0.0336

Gnomad4 ASJ exome

AF:

0.0365

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.152

Gnomad4 FIN exome

AF:

0.0721

Gnomad4 NFE exome

AF:

0.0680

Gnomad4 OTH exome

AF:

0.0712

GnomAD4 genome

AF:

0.0776

AC:

11645

AN:

150094

Hom.:

549

Cov.:

AF XY:

0.0801

AC XY:

5859

AN XY:

73186

show subpopulations

Gnomad4 AFR

AF:

0.0820

Gnomad4 AMR

AF:

0.0456

Gnomad4 ASJ

AF:

0.0351

Gnomad4 EAS

AF:

0.212

Gnomad4 SAS

AF:

0.164

Gnomad4 FIN

AF:

0.0682

Gnomad4 NFE

AF:

0.0702

Gnomad4 OTH

AF:

0.0522

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 26, 2011	274+26_274+27insGT in intron 4 of MYL2: This variant is not expected to have cl inical or pathological significance because it does not alter an amino acid resi due and is not located in the highly conserved region of the 5' splice site. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Sep 30, 2020

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over