12-110911079-A-G

Position:

• chr12-110911079-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4 PP5_Moderate

The NM_000432.4(MYL2):​c.499T>C​(p.Ter167GlnextTer?) variant causes a stop lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. *167*) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MYL2 NM_000432.4 stop_lost
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.62

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_000432.4 Downstream stopcodon found after 32 codons.
• PP5: Variant 12-110911079-A-G is Pathogenic according to our data. Variant chr12-110911079-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1162324.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL2	NM_000432.4	c.499T>C	p.Ter167GlnextTer?	stop_lost	7/7	ENST00000228841.15
MYL2	NM_001406745.1	c.457T>C	p.Ter153GlnextTer?	stop_lost	6/6
MYL2	NM_001406916.1	c.442T>C	p.Ter148GlnextTer?	stop_lost	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL2	ENST00000228841.15	c.499T>C	p.Ter167GlnextTer?	stop_lost	7/7	1	NM_000432.4	P1
MYL2	ENST00000548438.1	c.457T>C	p.Ter153GlnextTer?	stop_lost	6/6	3
MYL2	ENST00000663220.1	c.442T>C	p.Ter148GlnextTer?	stop_lost	7/7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital myopathy with fiber type disproportion Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Department of Pediatrics, The University of Tokyo

May 27, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.73
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.78	D
MutationTaster	Benign	1.0	N;N
Vest4		0.093
GERP RS		5.0

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-111348883;