Variant rs531661702 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_000432.4(MYL2):c.4-14delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,611,296 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

MYL2
NM_000432.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.820

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 12-110919206-AG-A is Benign according to our data. Variant chr12-110919206-AG-A is described in ClinVar as [Benign]. Clinvar id is 178888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-110919206-AG-A is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 144 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MYL2	NM_000432.4 linkuse as main transcript	c.4-14delC	intron_variant	ENST00000228841.15	NP_000423.2	P10916Q6IB42
MYL2	NM_001406745.1 linkuse as main transcript	c.4-14delC	intron_variant		NP_001393674.1
MYL2	NM_001406916.1 linkuse as main transcript	c.-54-14delC	intron_variant		NP_001393845.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MYL2	ENST00000228841.15 linkuse as main transcript	c.4-14delC	intron_variant	1	NM_000432.4	ENSP00000228841.8	P10916
MYL2	ENST00000548438.1 linkuse as main transcript	c.4-14delC	intron_variant	3		ENSP00000447154.1	G3V1V8
MYL2	ENST00000663220.1 linkuse as main transcript	c.-54-14delC	intron_variant			ENSP00000499568.1	A0A590UJU8
MYL2	ENST00000546404.1 linkuse as main transcript	c.4-14delC	intron_variant	2		ENSP00000499645.1	A0A590UK07

Frequencies

GnomAD3 genomes

AF:

0.000946

AC:

144

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000276

AC:

AN:

249818

Hom.:

AF XY:

0.000274

AC XY:

AN XY:

135058

show subpopulations

Gnomad AFR exome

AF:

0.00387

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000109

AC:

159

AN:

1459038

Hom.:

Cov.:

AF XY:

0.0000868

AC XY:

AN XY:

725842

show subpopulations

Gnomad4 AFR exome

AF:

0.00401

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000946

AC:

144

AN:

152258

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00320

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Bravo

AF:

0.00104

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypertrophic cardiomyopathy 10

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Apr 28, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -

Cardiomyopathy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Oct 16, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 21, 2013	The variant is found in HCM panel(s). -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 12, 2013

4-14delC in intron 1 of MYL2: This variant is not expected to have clinical sign ificance because it has been identified in 2.2% (94/4252) of African American ch romosomes by the NHLBI Exome Sequecing Project (http://evs.gs.washington.edu/EVS /). -

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