6-10529216-C-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_145649.5(GCNT2):c.305C>G(p.Thr102Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00934 in 1,614,172 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0079 ( 16 hom., cov: 32)
Exomes 𝑓: 0.0095 ( 103 hom. )
Consequence
GCNT2
NM_145649.5 missense
NM_145649.5 missense
Scores
4
11
Clinical Significance
Conservation
PhyloP100: 2.63
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0067899227).
BP6
?
Variant 6-10529216-C-G is Benign according to our data. Variant chr6-10529216-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1182271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00792 (1206/152310) while in subpopulation SAS AF= 0.0176 (85/4828). AF 95% confidence interval is 0.0146. There are 16 homozygotes in gnomad4. There are 597 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 16 BG,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GCNT2 | NM_145649.5 | c.305C>G | p.Thr102Ser | missense_variant | 3/5 | ENST00000495262.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GCNT2 | ENST00000495262.7 | c.305C>G | p.Thr102Ser | missense_variant | 3/5 | 2 | NM_145649.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00792 AC: 1206AN: 152192Hom.: 16 Cov.: 32
GnomAD3 genomes
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1206
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32
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GnomAD3 exomes AF: 0.00947 AC: 2381AN: 251454Hom.: 29 AF XY: 0.0103 AC XY: 1396AN XY: 135896
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GnomAD4 exome AF: 0.00949 AC: 13867AN: 1461862Hom.: 103 Cov.: 33 AF XY: 0.00980 AC XY: 7126AN XY: 727238
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GnomAD4 genome ? AF: 0.00792 AC: 1206AN: 152310Hom.: 16 Cov.: 32 AF XY: 0.00802 AC XY: 597AN XY: 74470
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30
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44
ESP6500AA
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9
ESP6500EA
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99
ExAC
?
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1204
Asia WGS
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21
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3478
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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
GCNT2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 05, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 09, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N;N
PROVEAN
Uncertain
N;N
REVEL
Benign
Sift4G
Uncertain
D;D
Polyphen
B;B
Vest4
MutPred
Loss of methylation at K105 (P = 0.1031);Loss of methylation at K105 (P = 0.1031);
MVP
MPC
0.046
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at