rs199758432
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_003289.4(TPM2):c.633G>A(p.Ala211=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
TPM2
NM_003289.4 synonymous
NM_003289.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.47
Genes affected
TPM2 (HGNC:12011): (tropomyosin 2) This gene encodes beta-tropomyosin, a member of the actin filament binding protein family, and mainly expressed in slow, type 1 muscle fibers. Mutations in this gene can alter the expression of other sarcomeric tropomyosin proteins, and cause cap disease, nemaline myopathy and distal arthrogryposis syndromes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
Variant 9-35684738-C-T is Benign according to our data. Variant chr9-35684738-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 528396.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.47 with no splicing effect.
BS2
?
High AC in GnomAd4 at 26 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPM2 | NM_003289.4 | c.633G>A | p.Ala211= | synonymous_variant | 6/9 | ENST00000645482.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPM2 | ENST00000645482.3 | c.633G>A | p.Ala211= | synonymous_variant | 6/9 | NM_003289.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152094Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000795 AC: 20AN: 251480Hom.: 0 AF XY: 0.0000809 AC XY: 11AN XY: 135914
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GnomAD4 exome AF: 0.000111 AC: 163AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.000129 AC XY: 94AN XY: 727246
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GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74408
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Arthrogryposis, distal, type 1A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at