6-10530003-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_145649.5(GCNT2):c.925+167A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 630,822 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (44 hom., cov: 32)
  • Exomes 𝑓: 0.022 (149 hom.)
• Consequence: GCNT2 NM_145649.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.521

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=-0.92).
• BP6: Variant 6-10530003-A-T is Benign according to our data. Variant chr6-10530003-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1215107.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0191 (2907/152320) while in subpopulation NFE AF= 0.0285 (1938/68032). AF 95% confidence interval is 0.0274. There are 44 homozygotes in gnomad4. There are 1397 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 44 BG,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCNT2	NM_145649.5	c.925+167A>T		intron_variant		ENST00000495262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCNT2	ENST00000495262.7	c.925+167A>T		intron_variant		2	NM_145649.5	P3

Frequencies

GnomAD3 genomes AF: 0.0191 AC: 2909 AN: 152202 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.00492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.0181

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.0224

GnomAD4 exome AF: 0.0222 AC: 10633 AN: 478502 Hom.: 149 Cov.: 5 AF XY: 0.0213 AC XY: 5394 AN XY: 253614

Gnomad4 AFR exome AF: 0.00524

Gnomad4 AMR exome AF: 0.0191

Gnomad4 ASJ exome AF: 0.0187

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00425

Gnomad4 FIN exome AF: 0.0232

Gnomad4 NFE exome AF: 0.0286

Gnomad4 OTH exome AF: 0.0227

GnomAD4 genome AF: 0.0191 AC: 2907 AN: 152320 Hom.: 44 Cov.: 32 AF XY: 0.0188 AC XY: 1397 AN XY: 74482

Gnomad4 AFR AF: 0.00491

Gnomad4 AMR AF: 0.0244

Gnomad4 ASJ AF: 0.0181

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0243

Gnomad4 NFE AF: 0.0285

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.00858 Hom.: 3

Bravo AF: 0.0193

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 24, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.88
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62397969; hg19: chr6-10530236;