rs3782889

chr12-110912851-A-G

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.402+245T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 152,116 control chromosomes in the GnomAD database, including 497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.073 (497 hom., cov: 33)
• Consequence: MYL2 NM_000432.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.582

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=-0.98).
• BP6: Variant 12-110912851-A-G is Benign according to our data. Variant chr12-110912851-A-G is described in ClinVar as [Benign]. Clinvar id is 1259772.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.402+245T>C		intron_variant		ENST00000228841.15
MYL2	NM_001406745.1	c.360+245T>C		intron_variant
MYL2	NM_001406916.1	c.345+245T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL2	ENST00000228841.15	c.402+245T>C		intron_variant		1	NM_000432.4	P1
MYL2	ENST00000548438.1	c.360+245T>C		intron_variant		3
MYL2	ENST00000663220.1	c.345+245T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11048 AN: 151998 Hom.: 498 Cov.: 33

Gnomad AFR AF: 0.0688

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0452

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0667

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0696

Gnomad OTH AF: 0.0484

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

GnomAD4 genome AF: 0.0726 AC: 11049 AN: 152116 Hom.: 497 Cov.: 33 AF XY: 0.0750 AC XY: 5577 AN XY: 74374

Gnomad4 AFR AF: 0.0689

Gnomad4 AMR AF: 0.0451

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0667

Gnomad4 NFE AF: 0.0696

Gnomad4 OTH AF: 0.0474

Alfa AF: 0.0682 Hom.: 571

Bravo AF: 0.0686

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.2
Dann	Benign	0.76

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: rs3782889; hg19: chr12-111350655;