Variant chr17-10543191-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000245503.10(MYH2):c.742-30A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,494,622 control chromosomes in the GnomAD database, including 149,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14265 hom., cov: 33)

Exomes 𝑓: 0.44 ( 135549 hom. )

Consequence

MYH2
ENST00000245503.10 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.761

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-10543191-T-G is Benign according to our data. Variant chr17-10543191-T-G is described in ClinVar as [Benign]. Clinvar id is 260828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MYH2	NM_017534.6 linkuse as main transcript	c.742-30A>C	intron_variant	ENST00000245503.10	NP_060004.3
MYHAS	NR_125367.1 linkuse as main transcript	n.168-24346T>G	intron_variant, non_coding_transcript_variant
MYH2	NM_001100112.2 linkuse as main transcript	c.742-30A>C	intron_variant		NP_001093582.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10 linkuse as main transcript	c.742-30A>C	intron_variant	1	NM_017534.6	ENSP00000245503	P1	Q9UKX2-1
MYH2	ENST00000532183.6 linkuse as main transcript	c.742-30A>C	intron_variant	1		ENSP00000433944		Q9UKX2-2
MYH2	ENST00000622564.4 linkuse as main transcript	c.742-30A>C	intron_variant	1		ENSP00000482463		Q9UKX2-2
MYH2	ENST00000397183.6 linkuse as main transcript	c.742-30A>C	intron_variant	5		ENSP00000380367	P1	Q9UKX2-1

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

63776

AN:

151938

Hom.:

14247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.454

Gnomad AMR

AF:

0.492

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.850

Gnomad SAS

AF:

0.619

Gnomad FIN

AF:

0.452

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.403

Gnomad OTH

AF:

0.415

GnomAD3 exomes

AF:

0.498

AC:

118309

AN:

237796

Hom.:

31773

AF XY:

0.495

AC XY:

63791

AN XY:

128948

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.619

Gnomad ASJ exome

AF:

0.461

Gnomad EAS exome

AF:

0.870

Gnomad SAS exome

AF:

0.607

Gnomad FIN exome

AF:

0.451

Gnomad NFE exome

AF:

0.409

Gnomad OTH exome

AF:

0.457

GnomAD4 exome

AF:

0.439

AC:

589729

AN:

1342566

Hom.:

135549

Cov.:

AF XY:

0.442

AC XY:

297690

AN XY:

672814

show subpopulations

Gnomad4 AFR exome

AF:

0.334

Gnomad4 AMR exome

AF:

0.599

Gnomad4 ASJ exome

AF:

0.456

Gnomad4 EAS exome

AF:

0.841

Gnomad4 SAS exome

AF:

0.604

Gnomad4 FIN exome

AF:

0.440

Gnomad4 NFE exome

AF:

0.406

Gnomad4 OTH exome

AF:

0.446

GnomAD4 genome

AF:

0.420

AC:

63839

AN:

152056

Hom.:

14265

Cov.:

AF XY:

0.432

AC XY:

32095

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.333

Gnomad4 AMR

AF:

0.492

Gnomad4 ASJ

AF:

0.448

Gnomad4 EAS

AF:

0.849

Gnomad4 SAS

AF:

0.618

Gnomad4 FIN

AF:

0.452

Gnomad4 NFE

AF:

0.403

Gnomad4 OTH

AF:

0.415

Alfa

AF:

0.405

Hom.:

3520

Bravo

AF:

0.418

Asia WGS

AF:

0.671

AC:

2314

AN:

3454

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Myopathy, proximal, and ophthalmoplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.5

DANN

Benign

0.84

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