chr12-110913199-AG-A

Position:

• chr12-110913199-AG-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_000432.4(MYL2):​c.353+46del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYL2 NM_000432.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 12-110913199-AG-A is Benign according to our data. Variant chr12-110913199-AG-A is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL2	NM_000432.4	c.353+46del		intron_variant		ENST00000228841.15	NP_000423.2
MYL2	NM_001406745.1	c.311+46del		intron_variant			NP_001393674.1
MYL2	NM_001406916.1	c.296+46del		intron_variant			NP_001393845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL2	ENST00000228841.15	c.353+46del		intron_variant		1	NM_000432.4	ENSP00000228841	P1
MYL2	ENST00000548438.1	c.311+46del		intron_variant		3		ENSP00000447154
MYL2	ENST00000663220.1	c.296+46del		intron_variant				ENSP00000499568
MYL2	ENST00000549029.1	n.230del		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

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: rs142220381; hg19: chr12-111351003;