6-10523593-G-C

Variant names:

• chr6-10523593-G-C
• rs1087924
• NM_145649.5:c.-469+2176G>C

Variant summary

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

The NM_145649.5(GCNT2):​c.-469+2176G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,826 control chromosomes in the GnomAD database, including 23,160 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 0.55 (23160 hom., cov: 31)
• Consequence: GCNT2 NM_145649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361
• Publications: 7 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCNT2	NM_145649.5	c.-469+2176G>C		intron_variant	Intron 1 of 4	ENST00000495262.7	NP_663624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCNT2	ENST00000495262.7	c.-469+2176G>C		intron_variant	Intron 1 of 4	2	NM_145649.5	ENSP00000419411.2

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83586 AN: 151708 Hom.: 23140 Cov.: 31

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.551 AC: 83648 AN: 151826 Hom.: 23160 Cov.: 31 AF XY: 0.554 AC XY: 41070 AN XY: 74196

African (AFR) AF: 0.562 AC: 23261 AN: 41384

American (AMR) AF: 0.539 AC: 8213 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2030 AN: 3470

East Asian (EAS) AF: 0.599 AC: 3079 AN: 5142

South Asian (SAS) AF: 0.711 AC: 3419 AN: 4810

European-Finnish (FIN) AF: 0.532 AC: 5606 AN: 10532

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36198 AN: 67934

Other (OTH) AF: 0.528 AC: 1115 AN: 2110

Alfa AF: 0.530 Hom.: 2571

Bravo AF: 0.546

Asia WGS AF: 0.609 AC: 2116 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	1.8
DANN	Benign	0.43
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1087924; hg19: chr6-10523826;