6-10621458-C-G
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The ENST00000316170.9(GCNT2):c.1012+15C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000357 in 1,541,272 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
GCNT2
ENST00000316170.9 intron
ENST00000316170.9 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.293
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 Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 6-10621458-C-G is Benign according to our data. Variant chr6-10621458-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 258156.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| GCNT2 | NM_001491.3 | c.1012+15C>G | intron_variant | ENST00000316170.9 | NP_001482.1 | |||
| GCNT2 | NM_145649.5 | c.1018+15C>G | intron_variant | ENST00000495262.7 | NP_663624.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| GCNT2 | ENST00000316170.9 | c.1012+15C>G | intron_variant | 1 | NM_001491.3 | ENSP00000314844 | ||||
| GCNT2 | ENST00000495262.7 | c.1018+15C>G | intron_variant | 2 | NM_145649.5 | ENSP00000419411 | P3 |
Frequencies
GnomAD3 genomes 0.0000329 AC: 5AN: 152170Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000141 AC: 35AN: 247644Hom.: 0 AF XY: 0.000112 AC XY: 15AN XY: 133840
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GnomAD4 exome AF: 0.0000360 AC: 50AN: 1388984Hom.: 0 Cov.: 23 AF XY: 0.0000317 AC XY: 22AN XY: 694880
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GnomAD4 genome 0.0000328 AC: 5AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74460
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Blood group, I system Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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DANN
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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