rs35537333

Variant names:

• chr6-10556753-G-A
• rs35537333
• NM_001491.3:c.330G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-10556753-G-A
• chr6-10556753-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001491.3(GCNT2):​c.330G>A​(p.Arg110Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 1,614,018 control chromosomes in the GnomAD database, including 519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (31 hom., cov: 32)
  • Exomes 𝑓: 0.024 (488 hom.)
• Consequence: GCNT2 NM_001491.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.157
• Publications: 4 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 6-10556753-G-A is Benign according to our data. Variant chr6-10556753-G-A is described in ClinVar as Benign. ClinVar VariationId is 354703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.157 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0167 (2539/152254) while in subpopulation NFE AF = 0.0265 (1805/68010). AF 95% confidence interval is 0.0255. There are 31 homozygotes in GnomAd4. There are 1209 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 31 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001491.3. 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_001491.3	MANE Plus Clinical	c.330G>A	p.Arg110Arg	synonymous	Exon 1 of 3	NP_001482.1	Q8N0V5-2
	GCNT2	NM_145649.5	MANE Select	c.925+26917G>A		intron	N/A	NP_663624.1	Q8N0V5-1
	GCNT2	NM_001374747.1		c.925+26917G>A		intron	N/A	NP_001361676.1	Q8N0V5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCNT2	ENST00000316170.9	TSL:1 MANE Plus Clinical	c.330G>A	p.Arg110Arg	synonymous	Exon 1 of 3	ENSP00000314844.3	Q8N0V5-2
	GCNT2	ENST00000495262.7	TSL:2 MANE Select	c.925+26917G>A		intron	N/A	ENSP00000419411.2	Q8N0V5-1
	GCNT2	ENST00000379597.7	TSL:1	c.925+26917G>A		intron	N/A	ENSP00000368917.3	Q8N0V5-1

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 2539 AN: 152136 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.00439

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00891

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0265

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.0169 AC: 4258 AN: 251298 AF XY: 0.0177

Gnomad AFR exome AF: 0.00443

Gnomad AMR exome AF: 0.00702

Gnomad ASJ exome AF: 0.00893

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0290

Gnomad NFE exome AF: 0.0244

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.0239 AC: 34992 AN: 1461764 Hom.: 488 Cov.: 33 AF XY: 0.0236 AC XY: 17198 AN XY: 727192

African (AFR) AF: 0.00338 AC: 113 AN: 33478

American (AMR) AF: 0.00742 AC: 332 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00803 AC: 210 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0123 AC: 1057 AN: 86254

European-Finnish (FIN) AF: 0.0289 AC: 1543 AN: 53416

Middle Eastern (MID) AF: 0.00485 AC: 28 AN: 5768

European-Non Finnish (NFE) AF: 0.0274 AC: 30434 AN: 1111894

Other (OTH) AF: 0.0211 AC: 1274 AN: 60394

GnomAD4 genome AF: 0.0167 AC: 2539 AN: 152254 Hom.: 31 Cov.: 32 AF XY: 0.0162 AC XY: 1209 AN XY: 74430

African (AFR) AF: 0.00438 AC: 182 AN: 41550

American (AMR) AF: 0.0120 AC: 184 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 24 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00892 AC: 43 AN: 4822

European-Finnish (FIN) AF: 0.0248 AC: 263 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0265 AC: 1805 AN: 68010

Other (OTH) AF: 0.0170 AC: 36 AN: 2114

Alfa AF: 0.0237 Hom.: 91

Bravo AF: 0.0150

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0237

EpiControl AF: 0.0213

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Blood group, I system (1)
-	-	1	Cataract 13 with adult I phenotype (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.72
PhyloP100		0.16
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: rs35537333; hg19: chr6-10556986;