6-10530003-A-T

Variant names:

• chr6-10530003-A-T
• rs62397969
• NM_145649.5:c.925+167A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.521
• Publications: 0 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, G2P, Labcorp Genetics (formerly Invitae)
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1215107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 44 AR,AD gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCNT2	NM_145649.5	MANE Select	c.925+167A>T		intron	N/A	NP_663624.1	Q8N0V5-1
	GCNT2	NM_001374747.1		c.925+167A>T		intron	N/A	NP_001361676.1	Q8N0V5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCNT2	ENST00000495262.7	TSL:2 MANE Select	c.925+167A>T		intron	N/A	ENSP00000419411.2	Q8N0V5-1
	GCNT2	ENST00000379597.7	TSL:1	c.925+167A>T		intron	N/A	ENSP00000368917.3	Q8N0V5-1
	GCNT2	ENST00000410107.5	TSL:1	c.67+20845A>T		intron	N/A	ENSP00000386321.1	B7ZBL3

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

African (AFR) AF: 0.00524 AC: 69 AN: 13170

American (AMR) AF: 0.0191 AC: 446 AN: 23314

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 281 AN: 15060

East Asian (EAS) AF: 0.00 AC: 0 AN: 30904

South Asian (SAS) AF: 0.00425 AC: 202 AN: 47506

European-Finnish (FIN) AF: 0.0232 AC: 675 AN: 29070

Middle Eastern (MID) AF: 0.0272 AC: 66 AN: 2424

European-Non Finnish (NFE) AF: 0.0286 AC: 8282 AN: 290058

Other (OTH) AF: 0.0227 AC: 612 AN: 26996

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

African (AFR) AF: 0.00491 AC: 204 AN: 41564

American (AMR) AF: 0.0244 AC: 373 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0181 AC: 63 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4832

European-Finnish (FIN) AF: 0.0243 AC: 258 AN: 10614

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0285 AC: 1938 AN: 68032

Other (OTH) AF: 0.0222 AC: 47 AN: 2116

Alfa AF: 0.00858 Hom.: 3

Bravo AF: 0.0193

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.88
DANN	Benign	0.59
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs62397969; hg19: chr6-10530236;