Variant rs56141211 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_145649.5(GCNT2):c.1049G>A(p.Gly350Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

GCNT2
NM_145649.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.22

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.904

PP5

Variant 6-10626447-G-A is Pathogenic according to our data. Variant chr6-10626447-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 9128.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-10626447-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCNT2	NM_145649.5 link	c.1049G>A	p.Gly350Glu	missense_variant	5/5	ENST00000495262.7	NP_663624.1	Q8N0V5-1
GCNT2	NM_001491.3 link	c.1043G>A	p.Gly348Glu	missense_variant	3/3	ENST00000316170.9	NP_001482.1	Q8N0V5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCNT2	ENST00000495262.7 link	c.1049G>A	p.Gly350Glu	missense_variant	5/5	2	NM_145649.5	ENSP00000419411.2		Q8N0V5-1
GCNT2	ENST00000316170.9 link	c.1043G>A	p.Gly348Glu	missense_variant	3/3	1	NM_001491.3	ENSP00000314844.3		Q8N0V5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

251338

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000652

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461386

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000731

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Cataract 13 with adult I phenotype

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 15, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

D;T;T;.;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

.;.;.;.;T

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.90

D;D;D;D;D

MetaSVM

Uncertain

0.46

MutationAssessor

Pathogenic

4.0

.;H;H;.;H

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-7.3

D;D;D;D;D

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0060

D;.;.;.;.

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;P;P;.;.

Vest4

0.97

MutPred

0.85

.;Loss of catalytic residue at D353 (P = 0.1067);Loss of catalytic residue at D353 (P = 0.1067);.;Loss of catalytic residue at D353 (P = 0.1067);

MVP

0.87

MPC

0.064

ClinPred

0.94

GERP RS

5.6

Varity_R

0.96

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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