rs17576994

Variant names:

• chr6-10599301-G-A
• rs17576994
• NM_145649.5:c.926-22050G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-10599301-G-A
• chr6-10599301-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145649.5(GCNT2):​c.926-22050G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,002 control chromosomes in the GnomAD database, including 18,806 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 0.50 (18806 hom., cov: 32)
• Consequence: GCNT2 NM_145649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352
• Publications: 2 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145649.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCNT2	NM_145649.5	MANE Select	c.926-22050G>A		intron	N/A	NP_663624.1
	GCNT2	NM_001491.3	MANE Plus Clinical	c.920-22050G>A		intron	N/A	NP_001482.1
	GCNT2	NM_001374747.1		c.926-22050G>A		intron	N/A	NP_001361676.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCNT2	ENST00000495262.7	TSL:2 MANE Select	c.926-22050G>A		intron	N/A	ENSP00000419411.2
	GCNT2	ENST00000316170.9	TSL:1 MANE Plus Clinical	c.920-22050G>A		intron	N/A	ENSP00000314844.3
	GCNT2	ENST00000265012.5	TSL:1	c.925+12387G>A		intron	N/A	ENSP00000265012.4

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75316 AN: 151884 Hom.: 18788 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.496 AC: 75377 AN: 152002 Hom.: 18806 Cov.: 32 AF XY: 0.502 AC XY: 37301 AN XY: 74320

African (AFR) AF: 0.497 AC: 20595 AN: 41438

American (AMR) AF: 0.624 AC: 9523 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1608 AN: 3464

East Asian (EAS) AF: 0.621 AC: 3216 AN: 5180

South Asian (SAS) AF: 0.473 AC: 2280 AN: 4824

European-Finnish (FIN) AF: 0.525 AC: 5544 AN: 10556

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31100 AN: 67958

Other (OTH) AF: 0.507 AC: 1071 AN: 2112

Alfa AF: 0.475 Hom.: 55119

Bravo AF: 0.506

Asia WGS AF: 0.540 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.76
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17576994; hg19: chr6-10599534;