rs41312812
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_003289.4(TPM2):c.375-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00958 in 1,614,122 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0059 ( 2 hom., cov: 32)
Exomes 𝑓: 0.010 ( 99 hom. )
Consequence
TPM2
NM_003289.4 intron
NM_003289.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.846
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 9-35685576-G-A is Benign according to our data. Variant chr9-35685576-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 259037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00592 (901/152242) while in subpopulation NFE AF= 0.0106 (722/67994). AF 95% confidence interval is 0.00998. There are 2 homozygotes in gnomad4. There are 401 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 901 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPM2 | NM_003289.4 | c.375-25C>T | intron_variant | ENST00000645482.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPM2 | ENST00000645482.3 | c.375-25C>T | intron_variant | NM_003289.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00592 AC: 901AN: 152124Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00677 AC: 1702AN: 251466Hom.: 12 AF XY: 0.00679 AC XY: 923AN XY: 135906
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GnomAD4 exome AF: 0.00996 AC: 14567AN: 1461880Hom.: 99 Cov.: 35 AF XY: 0.00982 AC XY: 7141AN XY: 727242
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GnomAD4 genome ? AF: 0.00592 AC: 901AN: 152242Hom.: 2 Cov.: 32 AF XY: 0.00539 AC XY: 401AN XY: 74452
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 28, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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