Genetic Variant NM_145649.5:c.925+44243T>C (chr6-10574079-T-C) – 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.925+44243T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,104 control chromosomes in the GnomAD database, including 24,215 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 0.56 ( 24215 hom., cov: 33)

Consequence

GCNT2
NM_145649.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0800

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:

Genome browser will be placed here

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=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCNT2	NM_145649.5 link	c.925+44243T>C		intron_variant	Intron 3 of 4	ENST00000495262.7	NP_663624.1
GCNT2	NM_001491.3 link	c.919+16737T>C		intron_variant	Intron 1 of 2	ENST00000316170.9	NP_001482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCNT2	ENST00000495262.7 link	c.925+44243T>C		intron_variant	Intron 3 of 4	2	NM_145649.5	ENSP00000419411.2
GCNT2	ENST00000316170.9 link	c.919+16737T>C		intron_variant	Intron 1 of 2	1	NM_001491.3	ENSP00000314844.3

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

85048

AN:

151986

Hom.:

24193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.463

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.641

Gnomad ASJ

AF:

0.656

Gnomad EAS

AF:

0.655

Gnomad SAS

AF:

0.656

Gnomad FIN

AF:

0.560

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.580

Gnomad OTH

AF:

0.599

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

GnomAD4 genome

AF:

0.560

AC:

85104

AN:

152104

Hom.:

24215

Cov.:

AF XY:

0.562

AC XY:

41803

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.463

AC:

19222

AN:

41494

American (AMR)

AF:

0.641

AC:

9801

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.656

AC:

2277

AN:

3472

East Asian (EAS)

AF:

0.655

AC:

3385

AN:

5164

South Asian (SAS)

AF:

0.656

AC:

3155

AN:

4808

European-Finnish (FIN)

AF:

0.560

AC:

5927

AN:

10578

Middle Eastern (MID)

AF:

0.673

AC:

198

AN:

294

European-Non Finnish (NFE)

AF:

0.580

AC:

39400

AN:

67980

Other (OTH)

AF:

0.594

AC:

1255

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1915

3830

5744

7659

9574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.572

Hom.:

48321

Bravo

AF:

0.562

Asia WGS

AF:

0.623

AC:

2166

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.5

(source)

DANN

Benign

0.70

PhyloP100

0.080

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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