rs933296

chr12-110915044-A-Cchr12-110915044-A-Gchr12-110915044-A-T

Variant summary

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

The NM_000432.4(MYL2):c.169+671T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,162 control chromosomes in the GnomAD database, including 42,897 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (42897 hom., cov: 32)
• Consequence: MYL2 NM_000432.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL2	NM_000432.4	c.169+671T>G		intron_variant		ENST00000228841.15
MYL2	NM_001406745.1	c.94-720T>G		intron_variant
MYL2	NM_001406916.1	c.112+671T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL2	ENST00000228841.15	c.169+671T>G		intron_variant		1	NM_000432.4	P1
MYL2	ENST00000548438.1	c.94-720T>G		intron_variant		3
MYL2	ENST00000663220.1	c.112+671T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.743 AC: 113006 AN: 152044 Hom.: 42846 Cov.: 32

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.708

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.743 AC: 113126 AN: 152162 Hom.: 42897 Cov.: 32 AF XY: 0.742 AC XY: 55197 AN XY: 74368

Gnomad4 AFR AF: 0.893

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.677

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.705

Alfa AF: 0.682 Hom.: 48177

Bravo AF: 0.752

Asia WGS AF: 0.695 AC: 2415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.21
Dann	Benign	0.71

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: rs933296; hg19: chr12-111352848;