17-10548996-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017534.6(MYH2):​c.-21+379T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,096 control chromosomes in the GnomAD database, including 14,161 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 14161 hom., cov: 33)

Consequence

MYH2
NM_017534.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.69
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYH2NM_017534.6 linkc.-21+379T>C intron_variant Intron 2 of 39 ENST00000245503.10 NP_060004.3 Q9UKX2-1
MYH2NM_001100112.2 linkc.-21+379T>C intron_variant Intron 2 of 39 NP_001093582.1 Q9UKX2-1
MYHASNR_125367.1 linkn.168-18541A>G intron_variant Intron 2 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYH2ENST00000245503.10 linkc.-21+379T>C intron_variant Intron 2 of 39 1 NM_017534.6 ENSP00000245503.5 Q9UKX2-1

Frequencies

GnomAD3 genomes
AF:
0.417
AC:
63410
AN:
151978
Hom.:
14144
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.323
Gnomad AMI
AF:
0.455
Gnomad AMR
AF:
0.491
Gnomad ASJ
AF:
0.448
Gnomad EAS
AF:
0.851
Gnomad SAS
AF:
0.618
Gnomad FIN
AF:
0.452
Gnomad MID
AF:
0.443
Gnomad NFE
AF:
0.403
Gnomad OTH
AF:
0.413
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.417
AC:
63472
AN:
152096
Hom.:
14161
Cov.:
33
AF XY:
0.429
AC XY:
31910
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.323
Gnomad4 AMR
AF:
0.492
Gnomad4 ASJ
AF:
0.448
Gnomad4 EAS
AF:
0.851
Gnomad4 SAS
AF:
0.618
Gnomad4 FIN
AF:
0.452
Gnomad4 NFE
AF:
0.403
Gnomad4 OTH
AF:
0.413
Alfa
AF:
0.412
Hom.:
12622
Bravo
AF:
0.415
Asia WGS
AF:
0.669
AC:
2324
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
11
DANN
Benign
0.76

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.

Other links and lift over

dbSNP: rs3760431; hg19: chr17-10452313; COSMIC: COSV55434408; COSMIC: COSV55434408; API