rs531661702

chr12-110919206-AG-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_000432.4(MYL2):c.4-14del variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.820

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.

• 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 GnomAd at 144 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL2	NM_000432.4	c.4-14del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000228841.15
MYL2	NM_001406745.1	c.4-14del		splice_polypyrimidine_tract_variant, intron_variant
MYL2	NM_001406916.1	c.-54-14del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL2	ENST00000228841.15	c.4-14del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000432.4	P1
MYL2	ENST00000546404.1	c.4-14del		splice_polypyrimidine_tract_variant, intron_variant		2
MYL2	ENST00000548438.1	c.4-14del		splice_polypyrimidine_tract_variant, intron_variant		3
MYL2	ENST00000663220.1	c.-54-14del		splice_polypyrimidine_tract_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.000946 AC: 144 AN: 152140 Hom.: 0 Cov.: 32

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: 69 AN: 249818 Hom.: 0 AF XY: 0.000274 AC XY: 37 AN XY: 135058

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.: 0 Cov.: 30 AF XY: 0.0000868 AC XY: 63 AN XY: 725842

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.: 0 Cov.: 32 AF XY: 0.00105 AC XY: 78 AN XY: 74460

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

Submissions by phenotype

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). -

Hypertrophic cardiomyopathy 10 Benign:2

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

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

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: rs531661702; hg19: chr12-111357010;