Variant rs2239933 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 NM_002470.4(MYH3):c.1003-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,613,298 control chromosomes in the GnomAD database, including 379,272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 27745 hom., cov: 30)

Exomes 𝑓: 0.68 ( 351527 hom. )

Consequence

MYH3
NM_002470.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.444

Variant links:

Genes affected

MYH3 (HGNC:7573): (myosin heavy chain 3) Myosin is a major contractile protein which converts chemical energy into mechanical energy through the hydrolysis of ATP. Myosin is a hexameric protein composed of a pair of myosin heavy chains (MYH) and two pairs of nonidentical light chains. This gene is a member of the MYH family and encodes a protein with an IQ domain and a myosin head-like domain. Mutations in this gene have been associated with two congenital contracture (arthrogryposis) syndromes, Freeman-Sheldon syndrome and Sheldon-Hall syndrome. [provided by RefSeq, Jul 2008]

MYH3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-10645867-G-A is Benign according to our data. Variant chr17-10645867-G-A is described in ClinVar as [Benign]. Clinvar id is 258667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
MYH3	NM_002470.4 linkuse as main transcript	c.1003-22C>T	intron_variant	ENST00000583535.6
MYH3	XM_011523870.4 linkuse as main transcript	c.1003-22C>T	intron_variant
MYH3	XM_011523871.3 linkuse as main transcript	c.1003-22C>T	intron_variant
MYH3	XM_047436127.1 linkuse as main transcript	c.1003-22C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH3	ENST00000583535.6 linkuse as main transcript	c.1003-22C>T		intron_variant		5	NM_002470.4	P1

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

86825

AN:

151556

Hom.:

27738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.743

Gnomad AMR

AF:

0.561

Gnomad ASJ

AF:

0.702

Gnomad EAS

AF:

0.359

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.708

Gnomad MID

AF:

0.545

Gnomad NFE

AF:

0.734

Gnomad OTH

AF:

0.591

GnomAD3 exomes

AF:

0.609

AC:

152995

AN:

251284

Hom.:

49611

AF XY:

0.621

AC XY:

84340

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.292

Gnomad AMR exome

AF:

0.466

Gnomad ASJ exome

AF:

0.706

Gnomad EAS exome

AF:

0.349

Gnomad SAS exome

AF:

0.538

Gnomad FIN exome

AF:

0.715

Gnomad NFE exome

AF:

0.728

Gnomad OTH exome

AF:

0.651

GnomAD4 exome

AF:

0.685

AC:

1000977

AN:

1461624

Hom.:

351527

Cov.:

AF XY:

0.684

AC XY:

497057

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.276

Gnomad4 AMR exome

AF:

0.479

Gnomad4 ASJ exome

AF:

0.704

Gnomad4 EAS exome

AF:

0.345

Gnomad4 SAS exome

AF:

0.539

Gnomad4 FIN exome

AF:

0.720

Gnomad4 NFE exome

AF:

0.729

Gnomad4 OTH exome

AF:

0.651

GnomAD4 genome

AF:

0.573

AC:

86857

AN:

151674

Hom.:

27745

Cov.:

AF XY:

0.568

AC XY:

42067

AN XY:

74088

show subpopulations

Gnomad4 AFR

AF:

0.294

Gnomad4 AMR

AF:

0.561

Gnomad4 ASJ

AF:

0.702

Gnomad4 EAS

AF:

0.360

Gnomad4 SAS

AF:

0.521

Gnomad4 FIN

AF:

0.708

Gnomad4 NFE

AF:

0.734

Gnomad4 OTH

AF:

0.595

Alfa

AF:

0.647

Hom.:

6913

Bravo

AF:

0.546

Asia WGS

AF:

0.460

AC:

1605

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Freeman-Sheldon syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Contractures, pterygia, and variable skeletal fusions syndrome 1B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Arthrogryposis, distal, type 2B3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A

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

-0.85

CADD

Benign

0.65

DANN

Benign

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over