rs145039915

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_017534.6(MYH2):​c.2106C>T​(p.Asn702=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000695 in 1,614,066 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00066 ( 9 hom. )

Consequence

MYH2
NM_017534.6 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.329
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]

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=-0.85).
BP6
Variant 17-10535147-G-A is Benign according to our data. Variant chr17-10535147-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 194975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.329 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 9 SD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MYH2NM_017534.6 linkuse as main transcriptc.2106C>T p.Asn702= synonymous_variant 19/40 ENST00000245503.10
MYHASNR_125367.1 linkuse as main transcriptn.168-32390G>A intron_variant, non_coding_transcript_variant
MYH2NM_001100112.2 linkuse as main transcriptc.2106C>T p.Asn702= synonymous_variant 19/40

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYH2ENST00000245503.10 linkuse as main transcriptc.2106C>T p.Asn702= synonymous_variant 19/401 NM_017534.6 P1Q9UKX2-1
ENST00000399342.6 linkuse as main transcriptn.370+1660G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00104
AC:
158
AN:
152070
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000266
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00249
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0172
Gnomad SAS
AF:
0.00187
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00269
AC:
676
AN:
251378
Hom.:
4
AF XY:
0.00224
AC XY:
305
AN XY:
135862
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00789
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0176
Gnomad SAS exome
AF:
0.00176
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00294
GnomAD4 exome
AF:
0.000661
AC:
966
AN:
1461878
Hom.:
9
Cov.:
32
AF XY:
0.000595
AC XY:
433
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.00720
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00922
Gnomad4 SAS exome
AF:
0.00145
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000477
Gnomad4 OTH exome
AF:
0.00147
GnomAD4 genome
AF:
0.00103
AC:
156
AN:
152188
Hom.:
1
Cov.:
32
AF XY:
0.00110
AC XY:
82
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.000265
Gnomad4 AMR
AF:
0.00248
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0169
Gnomad4 SAS
AF:
0.00187
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000223
Hom.:
0
Bravo
AF:
0.00162
Asia WGS
AF:
0.0120
AC:
43
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Myopathy, proximal, and ophthalmoplegia Benign:3
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsJan 13, 2022- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 21, 2024- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Feb 13, 2015- -
MYH2-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesFeb 06, 2020This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.90
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: rs145039915; hg19: chr17-10438464; API