dbSNP rs7223755: MYH2:c.5673+64G>A (chr17-10523026-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_017534.6(MYH2):c.5673+64G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 1,159,706 control chromosomes in the GnomAD database, including 182,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20850 hom., cov: 33)

Exomes 𝑓: 0.56 ( 161493 hom. )

Consequence

MYH2
NM_017534.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0890

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:

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.86).

BP6

Variant 17-10523026-C-T is Benign according to our data. Variant chr17-10523026-C-T is described in ClinVar as [Benign]. Clinvar id is 1260946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH2	NM_017534.6 link	c.5673+64G>A	intron_variant	Intron 39 of 39	ENST00000245503.10	NP_060004.3	Q9UKX2-1
MYH2	NM_001100112.2 link	c.5673+64G>A	intron_variant	Intron 39 of 39		NP_001093582.1	Q9UKX2-1
MYHAS	NR_125367.1 link	n.168-44511C>T	intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10 link	c.5673+64G>A		intron_variant	Intron 39 of 39	1	NM_017534.6	ENSP00000245503.5		Q9UKX2-1

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78046

AN:

151866

Hom.:

20834

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.428

Gnomad FIN

AF:

0.583

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.521

GnomAD4 exome

AF:

0.557

AC:

561634

AN:

1007722

Hom.:

161493

AF XY:

0.555

AC XY:

288807

AN XY:

520380

show subpopulations

Gnomad4 AFR exome

AF:

0.420

Gnomad4 AMR exome

AF:

0.403

Gnomad4 ASJ exome

AF:

0.569

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.438

Gnomad4 FIN exome

AF:

0.589

Gnomad4 NFE exome

AF:

0.602

Gnomad4 OTH exome

AF:

0.546

GnomAD4 genome

AF:

0.514

AC:

78114

AN:

151984

Hom.:

20850

Cov.:

AF XY:

0.507

AC XY:

37687

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.424

Gnomad4 AMR

AF:

0.464

Gnomad4 ASJ

AF:

0.569

Gnomad4 EAS

AF:

0.193

Gnomad4 SAS

AF:

0.428

Gnomad4 FIN

AF:

0.583

Gnomad4 NFE

AF:

0.598

Gnomad4 OTH

AF:

0.523

Alfa

AF:

0.547

Hom.:

3369

Bravo

AF:

0.501

Asia WGS

AF:

0.373

AC:

1302

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.8

DANN

Benign

0.24

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