rs2233260

chr12-110913195-G-Achr12-110913195-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.211

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL2	NM_000432.4	c.353+51C>T		intron_variant		ENST00000228841.15
MYL2	NM_001406745.1	c.311+51C>T		intron_variant
MYL2	NM_001406916.1	c.296+51C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL2	ENST00000228841.15	c.353+51C>T		intron_variant		1	NM_000432.4	P1
MYL2	ENST00000548438.1	c.311+51C>T		intron_variant		3
MYL2	ENST00000663220.1	c.296+51C>T		intron_variant
MYL2	ENST00000549029.1	n.235C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32017 AN: 151328 Hom.: 3690 Cov.: 33

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

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.: 38 AF XY: 0.227 AC XY: 164966 AN XY: 727160

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.: 33 AF XY: 0.210 AC XY: 15570 AN XY: 74050

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:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1 Other: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	- -

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

Other links and lift over

dbSNP: rs2233260; hg19: chr12-111350999; COSMIC: COSV57406861;