chr17-10547499-T-C

Position:

chr17-10547499-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000245503.10(MYH2):c.324A>G(p.Glu108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,613,458 control chromosomes in the GnomAD database, including 162,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15308 hom., cov: 31)

Exomes 𝑓: 0.44 ( 146858 hom. )

Consequence

MYH2
ENST00000245503.10 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 3.39

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 17-10547499-T-C is Benign according to our data. Variant chr17-10547499-T-C is described in ClinVar as [Benign]. Clinvar id is 260821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10547499-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=3.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYH2	NM_017534.6 linkuse as main transcript	c.324A>G	p.Glu108=	synonymous_variant	4/40	ENST00000245503.10	NP_060004.3
MYHAS	NR_125367.1 linkuse as main transcript	n.168-20038T>C		intron_variant, non_coding_transcript_variant
MYH2	NM_001100112.2 linkuse as main transcript	c.324A>G	p.Glu108=	synonymous_variant	4/40		NP_001093582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10 linkuse as main transcript	c.324A>G	p.Glu108=	synonymous_variant	4/40	1	NM_017534.6	ENSP00000245503	P1	Q9UKX2-1

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

66537

AN:

151796

Hom.:

15291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.387

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.449

Gnomad EAS

AF:

0.851

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.409

Gnomad OTH

AF:

0.429

GnomAD3 exomes

AF:

0.498

AC:

125230

AN:

251368

Hom.:

33588

AF XY:

0.496

AC XY:

67362

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.386

Gnomad AMR exome

AF:

0.613

Gnomad ASJ exome

AF:

0.454

Gnomad EAS exome

AF:

0.867

Gnomad SAS exome

AF:

0.598

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.409

Gnomad OTH exome

AF:

0.453

GnomAD4 exome

AF:

0.438

AC:

640398

AN:

1461542

Hom.:

146858

Cov.:

AF XY:

0.442

AC XY:

321338

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.379

Gnomad4 AMR exome

AF:

0.597

Gnomad4 ASJ exome

AF:

0.454

Gnomad4 EAS exome

AF:

0.840

Gnomad4 SAS exome

AF:

0.596

Gnomad4 FIN exome

AF:

0.438

Gnomad4 NFE exome

AF:

0.406

Gnomad4 OTH exome

AF:

0.447

GnomAD4 genome

AF:

0.438

AC:

66605

AN:

151916

Hom.:

15308

Cov.:

AF XY:

0.449

AC XY:

33329

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.388

Gnomad4 AMR

AF:

0.500

Gnomad4 ASJ

AF:

0.449

Gnomad4 EAS

AF:

0.850

Gnomad4 SAS

AF:

0.620

Gnomad4 FIN

AF:

0.450

Gnomad4 NFE

AF:

0.409

Gnomad4 OTH

AF:

0.429

Alfa

AF:

0.419

Hom.:

6198

Bravo

AF:

0.438

Asia WGS

AF:

0.675

AC:

2343

AN:

3478

EpiCase

AF:

0.408

EpiControl

AF:

0.413

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 08, 2015	- -

Myopathy, proximal, and ophthalmoplegia

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.82

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over