12-110914159-GACAC-GAC

Position:

• chr12-110914159-GACAC-GAC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_000432.4(MYL2):​c.274+25_274+26delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,182,930 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000047 (0 hom., cov: 31)
  • Exomes 𝑓: 0.016 (0 hom.)
• Consequence: MYL2 NM_000432.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.360

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 12-110914159-GAC-G is Benign according to our data. Variant chr12-110914159-GAC-G is described in ClinVar as [Benign]. Clinvar id is 1278892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-110914159-GAC-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0163 (16795/1032914) while in subpopulation NFE AF= 0.0179 (14114/788216). AF 95% confidence interval is 0.0177. There are 0 homozygotes in gnomad4_exome. There are 8124 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL2	NM_000432.4	c.274+25_274+26delGT		intron_variant		ENST00000228841.15	NP_000423.2
MYL2	NM_001406745.1	c.232+25_232+26delGT		intron_variant			NP_001393674.1
MYL2	NM_001406916.1	c.217+25_217+26delGT		intron_variant			NP_001393845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL2	ENST00000228841.15	c.274+25_274+26delGT		intron_variant		1	NM_000432.4	ENSP00000228841.8
MYL2	ENST00000548438.1	c.232+25_232+26delGT		intron_variant		3		ENSP00000447154.1
MYL2	ENST00000663220.1	c.217+25_217+26delGT		intron_variant				ENSP00000499568.1
MYL2	ENST00000549029.1	n.105+25_105+26delGT		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000467 AC: 7 AN: 149914 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000735

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000446

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0163 AC: 16795 AN: 1032914 Hom.: 0 AF XY: 0.0158 AC XY: 8124 AN XY: 514248

Gnomad4 AFR exome AF: 0.0150

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.0136

Gnomad4 EAS exome AF: 0.00852

Gnomad4 SAS exome AF: 0.00699

Gnomad4 FIN exome AF: 0.0121

Gnomad4 NFE exome AF: 0.0179

Gnomad4 OTH exome AF: 0.0146

GnomAD4 genome AF: 0.0000467 AC: 7 AN: 150016 Hom.: 0 Cov.: 31 AF XY: 0.0000547 AC XY: 4 AN XY: 73158

Gnomad4 AFR AF: 0.0000732

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000212

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000446

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0727 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cardiomyopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Aug 20, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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: rs142567411; hg19: chr12-111351963;