Variant rs2233260 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000432.4(MYL2):c.353+51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,613,166 control chromosomes in the GnomAD database, including 45,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3694 hom., cov: 33)

Exomes 𝑓: 0.23 ( 42096 hom. )

Consequence

MYL2
NM_000432.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

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:

MYL2 (HGNC:):

MYL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-110913195-G-A is Benign according to our data. Variant chr12-110913195-G-A is described in ClinVar as [Benign]. Clinvar id is 31774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-110913195-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MYL2	NM_000432.4 linkuse as main transcript	c.353+51C>T	intron_variant	ENST00000228841.15	NP_000423.2	P10916Q6IB42
MYL2	NM_001406745.1 linkuse as main transcript	c.311+51C>T	intron_variant		NP_001393674.1
MYL2	NM_001406916.1 linkuse as main transcript	c.296+51C>T	intron_variant		NP_001393845.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYL2	ENST00000228841.15 linkuse as main transcript	c.353+51C>T	intron_variant		1	NM_000432.4	ENSP00000228841.8	P10916
MYL2	ENST00000548438.1 linkuse as main transcript	c.311+51C>T	intron_variant		3		ENSP00000447154.1	G3V1V8
MYL2	ENST00000663220.1 linkuse as main transcript	c.296+51C>T	intron_variant				ENSP00000499568.1	A0A590UJU8
MYL2	ENST00000549029.1 linkuse as main transcript	n.235C>T	non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32017

AN:

151328

Hom.:

3690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.00423

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.245

Gnomad OTH

AF:

0.213

GnomAD3 exomes

AF:

0.210

AC:

52206

AN:

248922

Hom.:

6512

AF XY:

0.205

AC XY:

27540

AN XY:

134502

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.00273

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.234

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.232

AC:

338628

AN:

1461718

Hom.:

42096

Cov.:

AF XY:

0.227

AC XY:

164966

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.147

Gnomad4 AMR exome

AF:

0.322

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.00194

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.265

Gnomad4 NFE exome

AF:

0.249

Gnomad4 OTH exome

AF:

0.219

GnomAD4 genome

AF:

0.211

AC:

32023

AN:

151448

Hom.:

3694

Cov.:

AF XY:

0.210

AC XY:

15570

AN XY:

74050

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.279

Gnomad4 ASJ

AF:

0.110

Gnomad4 EAS

AF:

0.00444

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.275

Gnomad4 NFE

AF:

0.245

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.225

Hom.:

2827

Bravo

AF:

0.214

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
not provided, no classification provided	curation	Leiden Muscular Dystrophy (MYL2)	Mar 26, 2012	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.61

DANN

Benign

0.56

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