12-110913225-TCC-TC

Position:

• chr12-110913225-TCC-TC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000432.4(MYL2):​c.353+20delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,613,892 control chromosomes in the GnomAD database, including 77,478 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6317 hom., cov: 21)
  • Exomes 𝑓: 0.31 (71161 hom.)
• Consequence: MYL2 NM_000432.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11 O:1
• Conservation: PhyloP100: 0.00

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 12-110913225-TC-T is Benign according to our data. Variant chr12-110913225-TC-T is described in ClinVar as [Benign]. Clinvar id is 31772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-110913225-TC-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL2	NM_000432.4	c.353+20delG		intron_variant		ENST00000228841.15	NP_000423.2
MYL2	NM_001406745.1	c.311+20delG		intron_variant			NP_001393674.1
MYL2	NM_001406916.1	c.296+20delG		intron_variant			NP_001393845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL2	ENST00000228841.15	c.353+20delG		intron_variant		1	NM_000432.4	ENSP00000228841.8
MYL2	ENST00000548438.1	c.311+20delG		intron_variant		3		ENSP00000447154.1
MYL2	ENST00000663220.1	c.296+20delG		intron_variant				ENSP00000499568.1
MYL2	ENST00000549029.1	n.204delG		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43051 AN: 151988 Hom.: 6316 Cov.: 21

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.262

GnomAD3 exomes AF: 0.287 AC: 70480 AN: 245936 Hom.: 11151 AF XY: 0.285 AC XY: 37922 AN XY: 133110

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.353

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.208

Gnomad SAS exome AF: 0.248

Gnomad FIN exome AF: 0.331

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.283

GnomAD4 exome AF: 0.308 AC: 450939 AN: 1461786 Hom.: 71161 Cov.: 0 AF XY: 0.306 AC XY: 222296 AN XY: 727202

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.353

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.223

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.335

Gnomad4 NFE exome AF: 0.320

Gnomad4 OTH exome AF: 0.289

GnomAD4 genome AF: 0.283 AC: 43058 AN: 152106 Hom.: 6317 Cov.: 21 AF XY: 0.284 AC XY: 21132 AN XY: 74364

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.258

Alfa AF: 0.281 Hom.: 1140

Bravo AF: 0.280

ClinVar

Significance: Benign

Submissions summary: Benign:11 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hypertrophic cardiomyopathy 10 Benign:5

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 25, 2015	c.353+20delG in intron 5 of MYL2: This variant is not expected to have clinical significance because it has been identified in 29% (35041/121330) of chromosomes from multiple diverse populations by the Exome Aggregation Consortium (ExAC, ht tp://exac.broadinstitute.org; dbSNP rs3833910). -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:1 Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 11, 2018	- -
not provided, no classification provided	curation	Leiden Muscular Dystrophy (MYL2)	Mar 26, 2012	- -

Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Congestive heart failure Benign:1

Benign, criteria provided, single submitter

clinical testing

Cohesion Phenomics

Oct 10, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs3833910; hg19: chr12-111351029;