Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001491.3(GCNT2):c.741G>A(p.Ala247Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000578 in 1,548,304 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00039 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 18 hom. )

Consequence

GCNT2
NM_001491.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -6.17

Publications

0 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 6-10557164-G-A is Benign according to our data. Variant chr6-10557164-G-A is described in ClinVar as Benign. ClinVar VariationId is 258158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.17 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000394 (60/152218) while in subpopulation SAS AF = 0.0098 (47/4798). AF 95% confidence interval is 0.00757. There are 1 homozygotes in GnomAd4. There are 41 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 18 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001491.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GCNT2	NM_001491.3	MANE Plus Clinical	c.741G>A	p.Ala247Ala	synonymous	Exon 1 of 3	NP_001482.1
GCNT2	NM_145649.5	MANE Select	c.925+27328G>A		intron	N/A	NP_663624.1
GCNT2	NM_001374747.1		c.925+27328G>A		intron	N/A	NP_001361676.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GCNT2	ENST00000316170.9	TSL:1 MANE Plus Clinical	c.741G>A	p.Ala247Ala	synonymous	Exon 1 of 3	ENSP00000314844.3
GCNT2	ENST00000495262.7	TSL:2 MANE Select	c.925+27328G>A		intron	N/A	ENSP00000419411.2
GCNT2	ENST00000379597.7	TSL:1	c.925+27328G>A		intron	N/A	ENSP00000368917.3

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00958

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00110

AC:

214

AN:

195154

AF XY:

0.00137

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000412

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000192

Gnomad OTH exome

AF:

0.000881

GnomAD4 exome

AF:

0.000598

AC:

835

AN:

1396086

Hom.:

Cov.:

AF XY:

0.000872

AC XY:

600

AN XY:

688332

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31092

American (AMR)

AF:

0.0000299

AC:

AN:

33398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21580

East Asian (EAS)

AF:

0.0000255

AC:

AN:

39268

South Asian (SAS)

AF:

0.0100

AC:

737

AN:

73446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50800

Middle Eastern (MID)

AF:

0.00147

AC:

AN:

5446

European-Non Finnish (NFE)

AF:

0.0000443

AC:

AN:

1083534

Other (OTH)

AF:

0.000695

AC:

AN:

57522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

130

174

217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000394

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00980

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000257

Hom.:

Bravo

AF:

0.000106

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cataract 13 with adult I phenotype (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.0020

(source)

DANN

Benign

0.23

PhyloP100

-6.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs200874437

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over