rs2071629

Positions:

• chr12-110913382-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000432.4(MYL2):​c.275-58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 1,586,164 control chromosomes in the GnomAD database, including 5,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.072 (497 hom., cov: 33)
  • Exomes 𝑓: 0.077 (5007 hom.)
• Consequence: MYL2 NM_000432.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.0630

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL2	NM_000432.4	c.275-58G>A		intron_variant		ENST00000228841.15
MYL2	NM_001406745.1	c.233-58G>A		intron_variant
MYL2	NM_001406916.1	c.218-58G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL2	ENST00000228841.15	c.275-58G>A		intron_variant		1	NM_000432.4	P1
MYL2	ENST00000548438.1	c.233-58G>A		intron_variant		3
MYL2	ENST00000663220.1	c.218-58G>A		intron_variant
MYL2	ENST00000549029.1	n.106-58G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 11032 AN: 152106 Hom.: 498 Cov.: 33

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0451

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0664

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0695

Gnomad OTH AF: 0.0485

GnomAD4 exome AF: 0.0769 AC: 110203 AN: 1433940 Hom.: 5007 AF XY: 0.0789 AC XY: 56404 AN XY: 714928

Gnomad4 AFR exome AF: 0.0689

Gnomad4 AMR exome AF: 0.0310

Gnomad4 ASJ exome AF: 0.0347

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.0698

Gnomad4 NFE exome AF: 0.0711

Gnomad4 OTH exome AF: 0.0697

GnomAD4 genome AF: 0.0725 AC: 11033 AN: 152224 Hom.: 497 Cov.: 33 AF XY: 0.0748 AC XY: 5564 AN XY: 74412

Gnomad4 AFR AF: 0.0687

Gnomad4 AMR AF: 0.0450

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0664

Gnomad4 NFE AF: 0.0696

Gnomad4 OTH AF: 0.0475

Alfa AF: 0.0691 Hom.: 54

Bravo AF: 0.0685

Asia WGS AF: 0.111 AC: 385 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

Leiden Muscular Dystrophy (MYL2)

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.6
DANN	Benign	0.82

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: rs2071629; hg19: chr12-111351186;