Variant rs3744565 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_017534.6(MYH2):c.2697+25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,613,758 control chromosomes in the GnomAD database, including 155,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13792 hom., cov: 32)

Exomes 𝑓: 0.43 ( 142020 hom. )

Consequence

MYH2
NM_017534.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.280

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:

ENSG00000272736 (HGNC:):

ENSG00000272736 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=-0.89).

BP6

Variant 17-10531608-T-C is Benign according to our data. Variant chr17-10531608-T-C is described in ClinVar as [Benign]. Clinvar id is 260818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MYH2	NM_017534.6 linkuse as main transcript	c.2697+25A>G	intron_variant	ENST00000245503.10	NP_060004.3	Q9UKX2-1
MYH2	NM_001100112.2 linkuse as main transcript	c.2697+25A>G	intron_variant		NP_001093582.1	Q9UKX2-1
MYHAS	NR_125367.1 linkuse as main transcript	n.168-35929T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10 linkuse as main transcript	c.2697+25A>G		intron_variant		1	NM_017534.6	ENSP00000245503.5		Q9UKX2-1

Frequencies

GnomAD3 genomes

AF:

0.411

AC:

62519

AN:

151952

Hom.:

13781

Cov.:

show subpopulations

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.834

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.403

Gnomad OTH

AF:

0.408

GnomAD3 exomes

AF:

0.487

AC:

121864

AN:

250400

Hom.:

32125

AF XY:

0.486

AC XY:

65893

AN XY:

135474

show subpopulations

Gnomad AFR exome

AF:

0.302

Gnomad AMR exome

AF:

0.599

Gnomad ASJ exome

AF:

0.452

Gnomad EAS exome

AF:

0.849

Gnomad SAS exome

AF:

0.596

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.403

Gnomad OTH exome

AF:

0.443

GnomAD4 exome

AF:

0.430

AC:

628817

AN:

1461688

Hom.:

142020

Cov.:

AF XY:

0.434

AC XY:

315863

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.300

Gnomad4 AMR exome

AF:

0.583

Gnomad4 ASJ exome

AF:

0.453

Gnomad4 EAS exome

AF:

0.831

Gnomad4 SAS exome

AF:

0.594

Gnomad4 FIN exome

AF:

0.438

Gnomad4 NFE exome

AF:

0.400

Gnomad4 OTH exome

AF:

0.437

GnomAD4 genome

AF:

0.411

AC:

62564

AN:

152070

Hom.:

13792

Cov.:

AF XY:

0.424

AC XY:

31487

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.306

Gnomad4 AMR

AF:

0.488

Gnomad4 ASJ

AF:

0.448

Gnomad4 EAS

AF:

0.834

Gnomad4 SAS

AF:

0.615

Gnomad4 FIN

AF:

0.451

Gnomad4 NFE

AF:

0.403

Gnomad4 OTH

AF:

0.407

Alfa

AF:

0.413

Hom.:

13468

Bravo

AF:

0.408

Asia WGS

AF:

0.653

AC:

2267

AN:

3478

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

-0.89

CADD

Benign

6.0

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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