6-10528886-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145649.5(GCNT2):c.-26A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0739 in 1,539,366 control chromosomes in the GnomAD database, including 5,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.057 (370 hom., cov: 32)
  • Exomes 𝑓: 0.076 (4679 hom.)
• Consequence: GCNT2 NM_145649.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0690

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-10528886-A-C is Benign according to our data. Variant chr6-10528886-A-C is described in ClinVar as [Benign]. Clinvar id is 1285739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCNT2	NM_145649.5	c.-26A>C		5_prime_UTR_variant	3/5	ENST00000495262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCNT2	ENST00000495262.7	c.-26A>C		5_prime_UTR_variant	3/5	2	NM_145649.5	P3

Frequencies

GnomAD3 genomes AF: 0.0573 AC: 8724 AN: 152140 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.0789

GnomAD3 exomes AF: 0.0582 AC: 14605 AN: 251022 Hom.: 616 AF XY: 0.0594 AC XY: 8063 AN XY: 135818

Gnomad AFR exome AF: 0.0163

Gnomad AMR exome AF: 0.0464

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0240

Gnomad FIN exome AF: 0.0361

Gnomad NFE exome AF: 0.0841

Gnomad OTH exome AF: 0.0731

GnomAD4 exome AF: 0.0757 AC: 105007 AN: 1387108 Hom.: 4679 Cov.: 24 AF XY: 0.0747 AC XY: 51891 AN XY: 694592

Gnomad4 AFR exome AF: 0.0125

Gnomad4 AMR exome AF: 0.0490

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.000153

Gnomad4 SAS exome AF: 0.0237

Gnomad4 FIN exome AF: 0.0367

Gnomad4 NFE exome AF: 0.0870

Gnomad4 OTH exome AF: 0.0724

GnomAD4 genome AF: 0.0573 AC: 8719 AN: 152258 Hom.: 370 Cov.: 32 AF XY: 0.0536 AC XY: 3988 AN XY: 74444

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.0684

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.0333

Gnomad4 NFE AF: 0.0852

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0531 Hom.: 96

Bravo AF: 0.0594

Asia WGS AF: 0.00866 AC: 33 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.0
Dann	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs79945859; hg19: chr6-10529119; COSMIC: COSV65457025; COSMIC: COSV65457025;