chr6-10556639-C-T

Variant names:

• chr6-10556639-C-T
• rs2230906
• NM_001491.3:c.216C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001491.3(GCNT2):​c.216C>T​(p.Cys72Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,613,714 control chromosomes in the GnomAD database, including 12,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (894 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12037 hom.)
• Consequence: GCNT2 NM_001491.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.747
• Publications: 13 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 6-10556639-C-T is Benign according to our data. Variant chr6-10556639-C-T is described in ClinVar as Benign. ClinVar VariationId is 258157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.747 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

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.216C>T	p.Cys72Cys	synonymous	Exon 1 of 3	NP_001482.1
	GCNT2	NM_145649.5	MANE Select	c.925+26803C>T		intron	N/A	NP_663624.1
	GCNT2	NM_001374747.1		c.925+26803C>T		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.216C>T	p.Cys72Cys	synonymous	Exon 1 of 3	ENSP00000314844.3
	GCNT2	ENST00000495262.7	TSL:2 MANE Select	c.925+26803C>T		intron	N/A	ENSP00000419411.2
	GCNT2	ENST00000379597.7	TSL:1	c.925+26803C>T		intron	N/A	ENSP00000368917.3

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 15016 AN: 152096 Hom.: 894 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0657

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.0564

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.0997 AC: 25046 AN: 251270 AF XY: 0.101

Gnomad AFR exome AF: 0.0478

Gnomad AMR exome AF: 0.0437

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.0108

Gnomad FIN exome AF: 0.140

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.122 AC: 178565 AN: 1461500 Hom.: 12037 Cov.: 34 AF XY: 0.120 AC XY: 87547 AN XY: 727090

African (AFR) AF: 0.0461 AC: 1542 AN: 33476

American (AMR) AF: 0.0454 AC: 2030 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 5232 AN: 26136

East Asian (EAS) AF: 0.0100 AC: 398 AN: 39696

South Asian (SAS) AF: 0.0628 AC: 5418 AN: 86252

European-Finnish (FIN) AF: 0.146 AC: 7815 AN: 53420

Middle Eastern (MID) AF: 0.118 AC: 682 AN: 5766

European-Non Finnish (NFE) AF: 0.134 AC: 148458 AN: 1111652

Other (OTH) AF: 0.116 AC: 6990 AN: 60382

GnomAD4 genome AF: 0.0986 AC: 15011 AN: 152214 Hom.: 894 Cov.: 32 AF XY: 0.0980 AC XY: 7297 AN XY: 74424

African (AFR) AF: 0.0496 AC: 2059 AN: 41544

American (AMR) AF: 0.0655 AC: 1002 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3472

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5182

South Asian (SAS) AF: 0.0567 AC: 273 AN: 4816

European-Finnish (FIN) AF: 0.149 AC: 1577 AN: 10596

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8973 AN: 67992

Other (OTH) AF: 0.0996 AC: 210 AN: 2108

Alfa AF: 0.117 Hom.: 3854

Bravo AF: 0.0894

Asia WGS AF: 0.0290 AC: 100 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.127

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)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		0.75
Mutation Taster		=95/5	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2230906; hg19: chr6-10556872;