17-10529633-C-T
Position:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_017534.6(MYH2):c.3048G>A(p.Leu1016=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00077 in 1,614,140 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00073 ( 3 hom. )
Consequence
MYH2
NM_017534.6 synonymous
NM_017534.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.868
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 17-10529633-C-T is Benign according to our data. Variant chr17-10529633-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.868 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 3 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.3048G>A | p.Leu1016= | synonymous_variant | 24/40 | ENST00000245503.10 | |
MYHAS | NR_125367.1 | n.168-37904C>T | intron_variant, non_coding_transcript_variant | ||||
MYH2 | NM_001100112.2 | c.3048G>A | p.Leu1016= | synonymous_variant | 24/40 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH2 | ENST00000245503.10 | c.3048G>A | p.Leu1016= | synonymous_variant | 24/40 | 1 | NM_017534.6 | P1 | |
ENST00000399342.6 | n.207-3691C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00110 AC: 168AN: 152130Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
168
AN:
152130
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00109 AC: 275AN: 251430Hom.: 0 AF XY: 0.00120 AC XY: 163AN XY: 135892
GnomAD3 exomes
AF:
AC:
275
AN:
251430
Hom.:
AF XY:
AC XY:
163
AN XY:
135892
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000734 AC: 1073AN: 1461892Hom.: 3 Cov.: 34 AF XY: 0.000800 AC XY: 582AN XY: 727248
GnomAD4 exome
AF:
AC:
1073
AN:
1461892
Hom.:
Cov.:
34
AF XY:
AC XY:
582
AN XY:
727248
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00112 AC: 170AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.00101 AC XY: 75AN XY: 74448
GnomAD4 genome
AF:
AC:
170
AN:
152248
Hom.:
Cov.:
32
AF XY:
AC XY:
75
AN XY:
74448
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | MYH2: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 28, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Myopathy, proximal, and ophthalmoplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at