6-10529216-C-G

Variant names:

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.63

Variant links:

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]

GCNT2 links:

Genome browser will be placed here

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 GnomAd4 at 16 BG,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCNT2	NM_145649.5 link	c.305C>G	p.Thr102Ser	missense_variant	Exon 3 of 5	ENST00000495262.7	NP_663624.1	Q8N0V5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCNT2	ENST00000495262.7 link	c.305C>G	p.Thr102Ser	missense_variant	Exon 3 of 5	2	NM_145649.5	ENSP00000419411.2		Q8N0V5-1

Frequencies

GnomAD3 genomes

AF:

0.00792

AC:

1206

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.00818

Gnomad ASJ

AF:

0.0265

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.0138

GnomAD3 exomes

AF:

0.00947

AC:

2381

AN:

251454

Hom.:

AF XY:

0.0103

AC XY:

1396

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00653

Gnomad ASJ exome

AF:

0.0273

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0188

Gnomad FIN exome

AF:

0.00319

Gnomad NFE exome

AF:

0.00994

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.00949

AC:

13867

AN:

1461862

Hom.:

103

Cov.:

AF XY:

0.00980

AC XY:

7126

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00704

Gnomad4 ASJ exome

AF:

0.0280

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0191

Gnomad4 FIN exome

AF:

0.00316

Gnomad4 NFE exome

AF:

0.00922

Gnomad4 OTH exome

AF:

0.0100

GnomAD4 genome

AF:

0.00792

AC:

1206

AN:

152310

Hom.:

Cov.:

AF XY:

0.00802

AC XY:

597

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00817

Gnomad4 ASJ

AF:

0.0265

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0176

Gnomad4 FIN

AF:

0.00301

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.00780

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0115

AC:

ExAC

AF:

0.00992

AC:

1204

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0125

EpiControl

AF:

0.0121

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 09, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GCNT2-related disorder

Benign:1

Mar 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.049

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.79

MetaRNN

Benign

0.0068

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.7

M;M

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.18

Sift4G

Uncertain

0.018

D;D

Polyphen

0.11

B;B

Vest4

0.50

MutPred

0.72

Loss of methylation at K105 (P = 0.1031);Loss of methylation at K105 (P = 0.1031);

MVP

0.37

MPC

0.046

ClinPred

0.040

GERP RS

3.3

Varity_R

0.71

gMVP

0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over