rs35838082
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000215838.8(TCN2):c.643C>A(p.Arg215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,076 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
TCN2
ENST00000215838.8 synonymous
ENST00000215838.8 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.61
Genes affected
TCN2 (HGNC:11653): (transcobalamin 2) This gene encodes a member of the vitamin B12-binding protein family. This family of proteins, alternatively referred to as R binders, is expressed in various tissues and secretions. This plasma protein binds cobalamin and mediates the transport of cobalamin into cells. This protein and other mammalian cobalamin-binding proteins, such as transcobalamin I and gastric intrisic factor, may have evolved by duplication of a common ancestral gene. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TCN2 | NM_000355.4 | c.643C>A | p.Arg215= | synonymous_variant | 5/9 | ENST00000215838.8 | NP_000346.2 | |
TCN2 | NM_001184726.2 | c.562C>A | p.Arg188= | synonymous_variant | 5/9 | NP_001171655.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TCN2 | ENST00000215838.8 | c.643C>A | p.Arg215= | synonymous_variant | 5/9 | 1 | NM_000355.4 | ENSP00000215838 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152076Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 32
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152076Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74278
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Transcobalamin II deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 25, 2022 | This sequence change affects codon 215 of the TCN2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the TCN2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TCN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1013711). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at