Variant 12-110913199-AG-AGG 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.353+46_353+47insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0773 in 1,593,392 control chromosomes in the GnomAD database, including 5,554 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 495 hom., cov: 32)

Exomes 𝑓: 0.077 ( 5059 hom. )

Consequence

MYL2
NM_000432.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -0.228

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 12-110913199-A-AG is Benign according to our data. Variant chr12-110913199-A-AG is described in ClinVar as [Benign]. Clinvar id is 31775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MYL2	NM_000432.4 linkuse as main transcript	c.353+46_353+47insC	intron_variant	ENST00000228841.15	NP_000423.2
MYL2	NM_001406745.1 linkuse as main transcript	c.311+46_311+47insC	intron_variant		NP_001393674.1
MYL2	NM_001406916.1 linkuse as main transcript	c.296+46_296+47insC	intron_variant		NP_001393845.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
MYL2	ENST00000228841.15 linkuse as main transcript	c.353+46_353+47insC	intron_variant		1	NM_000432.4	ENSP00000228841	P1
MYL2	ENST00000548438.1 linkuse as main transcript	c.311+46_311+47insC	intron_variant		3		ENSP00000447154
MYL2	ENST00000663220.1 linkuse as main transcript	c.296+46_296+47insC	intron_variant				ENSP00000499568
MYL2	ENST00000549029.1 linkuse as main transcript	n.230_231insC	non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0784

AC:

11027

AN:

140630

Hom.:

496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0873

Gnomad AMI

AF:

0.0734

Gnomad AMR

AF:

0.0479

Gnomad ASJ

AF:

0.0346

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.0691

Gnomad MID

AF:

0.0649

Gnomad NFE

AF:

0.0706

Gnomad OTH

AF:

0.0515

GnomAD3 exomes

AF:

0.0742

AC:

18258

AN:

245936

Hom.:

1186

AF XY:

0.0778

AC XY:

10352

AN XY:

133050

show subpopulations

Gnomad AFR exome

AF:

0.0576

Gnomad AMR exome

AF:

0.0237

Gnomad ASJ exome

AF:

0.0303

Gnomad EAS exome

AF:

0.213

Gnomad SAS exome

AF:

0.123

Gnomad FIN exome

AF:

0.0647

Gnomad NFE exome

AF:

0.0647

Gnomad OTH exome

AF:

0.0590

GnomAD4 exome

AF:

0.0772

AC:

112089

AN:

1452666

Hom.:

5059

Cov.:

AF XY:

0.0791

AC XY:

57214

AN XY:

723320

show subpopulations

Gnomad4 AFR exome

AF:

0.0881

Gnomad4 AMR exome

AF:

0.0313

Gnomad4 ASJ exome

AF:

0.0348

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.0699

Gnomad4 NFE exome

AF:

0.0710

Gnomad4 OTH exome

AF:

0.0709

GnomAD4 genome

AF:

0.0784

AC:

11028

AN:

140726

Hom.:

495

Cov.:

AF XY:

0.0808

AC XY:

5565

AN XY:

68862

show subpopulations

Gnomad4 AFR

AF:

0.0875

Gnomad4 AMR

AF:

0.0477

Gnomad4 ASJ

AF:

0.0346

Gnomad4 EAS

AF:

0.211

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.0691

Gnomad4 NFE

AF:

0.0706

Gnomad4 OTH

AF:

0.0504

Alfa

AF:

0.0694

Hom.:

Bravo

AF:

0.0684

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

not provided, no classification provided	curation	Leiden Muscular Dystrophy (MYL2)	Mar 26, 2012	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Primary familial hypertrophic cardiomyopathy

Benign:1

Benign, no assertion criteria provided

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Apr 28, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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