Genetic Variant GCNT2:c.926-22305T>G (chr6-10599046-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145649.5(GCNT2):c.926-22305T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,158 control chromosomes in the GnomAD database, including 1,099 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1099 hom., cov: 32)

Consequence

GCNT2
NM_145649.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.862

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

cataract 13 with adult I phenotype
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
total early-onset cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GCNT2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCNT2	NM_145649.5 link	c.926-22305T>G		intron_variant	Intron 3 of 4	ENST00000495262.7	NP_663624.1	Q8N0V5-1
GCNT2	NM_001491.3 link	c.920-22305T>G		intron_variant	Intron 1 of 2	ENST00000316170.9	NP_001482.1	Q8N0V5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCNT2	ENST00000495262.7 link	c.926-22305T>G		intron_variant	Intron 3 of 4	2	NM_145649.5	ENSP00000419411.2		Q8N0V5-1
GCNT2	ENST00000316170.9 link	c.920-22305T>G		intron_variant	Intron 1 of 2	1	NM_001491.3	ENSP00000314844.3		Q8N0V5-2

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16736

AN:

152040

Hom.:

1099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0602

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.0781

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.00520

Gnomad SAS

AF:

0.0619

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.102

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.110

AC:

16735

AN:

152158

Hom.:

1099

Cov.:

AF XY:

0.108

AC XY:

8029

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0601

AC:

2495

AN:

41510

American (AMR)

AF:

0.0779

AC:

1189

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

571

AN:

3470

East Asian (EAS)

AF:

0.00521

AC:

AN:

5182

South Asian (SAS)

AF:

0.0622

AC:

300

AN:

4824

European-Finnish (FIN)

AF:

0.149

AC:

1573

AN:

10590

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.150

AC:

10206

AN:

67998

Other (OTH)

AF:

0.100

AC:

211

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

757

1514

2271

3028

3785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.124

Hom.:

2404

Bravo

AF:

0.102

Asia WGS

AF:

0.0390

AC:

135

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.85

(source)

DANN

Benign

0.37

PhyloP100

-0.86

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over