rs28645088

Positions:

• chr12-110913320-C-A
• chr12-110913320-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000432.4(MYL2):​c.279G>T​(p.Ala93Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A93A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYL2 NM_000432.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL2	NM_000432.4	c.279G>T	p.Ala93Ala	synonymous_variant	5/7	ENST00000228841.15	NP_000423.2
MYL2	NM_001406745.1	c.237G>T	p.Ala79Ala	synonymous_variant	4/6		NP_001393674.1
MYL2	NM_001406916.1	c.222G>T	p.Ala74Ala	synonymous_variant	5/7		NP_001393845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL2	ENST00000228841.15	c.279G>T	p.Ala93Ala	synonymous_variant	5/7	1	NM_000432.4	ENSP00000228841.8
MYL2	ENST00000548438.1	c.237G>T	p.Ala79Ala	synonymous_variant	4/6	3		ENSP00000447154.1
MYL2	ENST00000663220.1	c.222G>T	p.Ala74Ala	synonymous_variant	5/7			ENSP00000499568.1
MYL2	ENST00000549029.1	n.110G>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.69
DANN	Benign	0.69

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: rs28645088; hg19: chr12-111351124;