Variant 17-10547728-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_017534.6(MYH2):c.193G>A(p.Glu65Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MYH2
NM_017534.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.72

Variant links:

Genes affected

MYH2 (HGNC:7572): (myosin heavy chain 2) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in inclusion body myopathy-3. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2009]

MYH2 links:

MYHAS (HGNC:):

MYHAS links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MYH2. . Gene score misZ 1.9724 (greater than the threshold 3.09). Trascript score misZ 4.733 (greater than threshold 3.09). GenCC has associacion of gene with childhood-onset autosomal recessive myopathy with external ophthalmoplegia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, myopathy, proximal, and ophthalmoplegia.

BP4

Computational evidence support a benign effect (MetaRNN=0.26992112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH2	NM_017534.6 linkuse as main transcript	c.193G>A	p.Glu65Lys	missense_variant	3/40	ENST00000245503.10	NP_060004.3	Q9UKX2-1
MYH2	NM_001100112.2 linkuse as main transcript	c.193G>A	p.Glu65Lys	missense_variant	3/40		NP_001093582.1	Q9UKX2-1
MYHAS	NR_125367.1 linkuse as main transcript	n.168-19809C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10 linkuse as main transcript	c.193G>A	p.Glu65Lys	missense_variant	3/40	1	NM_017534.6	ENSP00000245503.5		Q9UKX2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251418

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

.;T;T;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.065

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.92

.;.;D;D;D

M_CAP

Benign

0.034

MetaRNN

Benign

0.27

T;T;T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.9

L;L;L;L;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.2

N;N;N;.;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.020

D;T;T;.;D

Sift4G

Benign

0.31

T;T;T;T;.

Polyphen

0.0030

.;B;B;.;.

Vest4

0.46

MutPred

0.41

Gain of MoRF binding (P = 0.0052);Gain of MoRF binding (P = 0.0052);Gain of MoRF binding (P = 0.0052);Gain of MoRF binding (P = 0.0052);Gain of MoRF binding (P = 0.0052);

MVP

0.76

MPC

1.2

ClinPred

0.30

GERP RS

5.7

Varity_R

0.26

gMVP

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over