6-10557110-T-C

Variant names:

• chr6-10557110-T-C
• rs35318346
• NM_001491.3:c.687T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001491.3(GCNT2):​c.687T>C​(p.Tyr229Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,564,624 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00065 (12 hom.)
• Consequence: GCNT2 NM_001491.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.961
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 6-10557110-T-C is Benign according to our data. Variant chr6-10557110-T-C is described in ClinVar as Benign. ClinVar VariationId is 354707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.961 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00611 (930/152310) while in subpopulation AFR AF = 0.021 (874/41564). AF 95% confidence interval is 0.0199. There are 12 homozygotes in GnomAd4. There are 418 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 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.687T>C	p.Tyr229Tyr	synonymous	Exon 1 of 3	NP_001482.1
	GCNT2	NM_145649.5	MANE Select	c.925+27274T>C		intron	N/A	NP_663624.1
	GCNT2	NM_001374747.1		c.925+27274T>C		intron	N/A	NP_001361676.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCNT2	ENST00000316170.9	TSL:1 MANE Plus Clinical	c.687T>C	p.Tyr229Tyr	synonymous	Exon 1 of 3	ENSP00000314844.3
	GCNT2	ENST00000495262.7	TSL:2 MANE Select	c.925+27274T>C		intron	N/A	ENSP00000419411.2
	GCNT2	ENST00000379597.7	TSL:1	c.925+27274T>C		intron	N/A	ENSP00000368917.3

Frequencies

GnomAD3 genomes AF: 0.00611 AC: 930 AN: 152192 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00190 AC: 388 AN: 203686 AF XY: 0.00135

Gnomad AFR exome AF: 0.0219

Gnomad AMR exome AF: 0.00125

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000598

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.00106

GnomAD4 exome AF: 0.000654 AC: 923 AN: 1412314 Hom.: 12 Cov.: 33 AF XY: 0.000569 AC XY: 398 AN XY: 698958

African (AFR) AF: 0.0228 AC: 719 AN: 31532

American (AMR) AF: 0.00120 AC: 43 AN: 35748

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22476

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39494

South Asian (SAS) AF: 0.0000917 AC: 7 AN: 76328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51182

Middle Eastern (MID) AF: 0.00238 AC: 13 AN: 5472

European-Non Finnish (NFE) AF: 0.0000403 AC: 44 AN: 1091906

Other (OTH) AF: 0.00165 AC: 96 AN: 58176

GnomAD4 genome AF: 0.00611 AC: 930 AN: 152310 Hom.: 12 Cov.: 32 AF XY: 0.00561 AC XY: 418 AN XY: 74466

African (AFR) AF: 0.0210 AC: 874 AN: 41564

American (AMR) AF: 0.00268 AC: 41 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68032

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00292 Hom.: 4

Bravo AF: 0.00733

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.64
CADD	Benign	0.069
DANN	Benign	0.23
PhyloP100		-0.96
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: rs35318346; hg19: chr6-10557343;