rs1085307067
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001491.3(GCNT2):c.259_262del(p.Ser87ArgfsTer11) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
GCNT2
NM_001491.3 frameshift
NM_001491.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.76
Genes affected
GCNT2 (HGNC:4204): (glucosaminyl (N-acetyl) transferase 2 (I blood group)) This gene encodes the enzyme responsible for formation of the blood group I antigen. The i and I antigens are distinguished by linear and branched poly-N-acetyllactosaminoglycans, respectively. The encoded protein is the I-branching enzyme, a beta-1,6-N-acetylglucosaminyltransferase responsible for the conversion of fetal i antigen to adult I antigen in erythrocytes during embryonic development. Mutations in this gene have been associated with adult i blood group phenotype. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| GCNT2 | NM_001491.3 | c.259_262del | p.Ser87ArgfsTer11 | frameshift_variant | 1/3 | ENST00000316170.9 | |
| GCNT2 | NM_145649.5 | c.925+26846_925+26849del | intron_variant | ENST00000495262.7 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GCNT2 | ENST00000316170.9 | c.259_262del | p.Ser87ArgfsTer11 | frameshift_variant | 1/3 | 1 | NM_001491.3 | ||
| GCNT2 | ENST00000495262.7 | c.925+26846_925+26849del | intron_variant | 2 | NM_145649.5 | P3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251224Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135768
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461848Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727242
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Blood group, I system;C3805373:Cataract 13 with adult I phenotype Uncertain:1
| Uncertain significance, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at