chr2-1414489-A-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001206744.2(TPO):āc.81A>Gā(p.Lys27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,940 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 (ā ).
Frequency
Genomes: š 0.000072 ( 0 hom., cov: 33)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
TPO
NM_001206744.2 synonymous
NM_001206744.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.373
Genes affected
TPO (HGNC:12015): (thyroid peroxidase) This gene encodes a membrane-bound glycoprotein. The encoded protein acts as an enzyme and plays a central role in thyroid gland function. The protein functions in the iodination of tyrosine residues in thyroglobulin and phenoxy-ester formation between pairs of iodinated tyrosines to generate the thyroid hormones, thyroxine and triiodothyronine. Mutations in this gene are associated with several disorders of thyroid hormonogenesis, including congenital hypothyroidism, congenital goiter, and thyroid hormone organification defect IIA. Multiple transcript variants encoding distinct isoforms have been identified for this gene, but the full-length nature of some variants has not been determined. [provided by RefSeq, May 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 2-1414489-A-G is Benign according to our data. Variant chr2-1414489-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2905518.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.373 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPO | NM_001206744.2 | c.81A>G | p.Lys27= | synonymous_variant | 2/17 | ENST00000329066.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPO | ENST00000329066.9 | c.81A>G | p.Lys27= | synonymous_variant | 2/17 | 1 | NM_001206744.2 | P1 | |
ENST00000650512.1 | n.646+3874T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152210Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251132Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135758
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461730Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727140
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74374
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 29, 2023 | - - |
Computational scores
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at