Variant chr12-110911079-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM4PP5_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

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 6.62

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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
MYL2	NM_000432.4 linkuse as main transcript	c.499T>C	p.Ter167GlnextTer?	stop_lost	7/7	ENST00000228841.15
MYL2	NM_001406745.1 linkuse as main transcript	c.457T>C	p.Ter153GlnextTer?	stop_lost	6/6
MYL2	NM_001406916.1 linkuse as main transcript	c.442T>C	p.Ter148GlnextTer?	stop_lost	7/7

Ensembl

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

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

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.73

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.78

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over