Genetic Variant NM_017534.6:c.1148-98A>G (chr17-10539660-T-C) – 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.1148-98A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 1,319,806 control chromosomes in the GnomAD database, including 132,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14261 hom., cov: 32)

Exomes 𝑓: 0.44 ( 117928 hom. )

Consequence

MYH2
NM_017534.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.354

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: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=-0.85).

BP6

Variant 17-10539660-T-C is Benign according to our data. Variant chr17-10539660-T-C is described in ClinVar as [Benign]. Clinvar id is 1175449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH2	NM_017534.6 link	c.1148-98A>G	intron_variant	Intron 12 of 39	ENST00000245503.10	NP_060004.3	Q9UKX2-1
MYH2	NM_001100112.2 link	c.1148-98A>G	intron_variant	Intron 12 of 39		NP_001093582.1	Q9UKX2-1
MYHAS	NR_125367.1 link	n.168-27877T>C	intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH2	ENST00000245503.10 link	c.1148-98A>G		intron_variant	Intron 12 of 39	1	NM_017534.6	ENSP00000245503.5		Q9UKX2-1

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

63748

AN:

151896

Hom.:

14243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.492

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.851

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.403

Gnomad OTH

AF:

0.416

GnomAD4 exome

AF:

0.439

AC:

512271

AN:

1167792

Hom.:

117928

AF XY:

0.443

AC XY:

262252

AN XY:

592050

show subpopulations

Gnomad4 AFR exome

AF:

0.330

Gnomad4 AMR exome

AF:

0.586

Gnomad4 ASJ exome

AF:

0.453

Gnomad4 EAS exome

AF:

0.839

Gnomad4 SAS exome

AF:

0.596

Gnomad4 FIN exome

AF:

0.438

Gnomad4 NFE exome

AF:

0.403

Gnomad4 OTH exome

AF:

0.443

GnomAD4 genome

AF:

0.420

AC:

63811

AN:

152014

Hom.:

14261

Cov.:

AF XY:

0.431

AC XY:

32041

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.492

Gnomad4 ASJ

AF:

0.448

Gnomad4 EAS

AF:

0.850

Gnomad4 SAS

AF:

0.618

Gnomad4 FIN

AF:

0.450

Gnomad4 NFE

AF:

0.404

Gnomad4 OTH

AF:

0.416

Alfa

AF:

0.402

Hom.:

2024

Bravo

AF:

0.418

Asia WGS

AF:

0.671

AC:

2331

AN:

3478

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 15, 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

-0.85

CADD

Benign

3.5

DANN

Benign

0.50

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