6-10528886-A-C

Variant names:

• chr6-10528886-A-C
• rs79945859
• NM_145649.5:c.-26A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145649.5(GCNT2):​c.-26A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0739 in 1,539,366 control chromosomes in the GnomAD database, including 5,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.057 (370 hom., cov: 32)
  • Exomes 𝑓: 0.076 (4679 hom.)
• Consequence: GCNT2 NM_145649.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0690
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-10528886-A-C is Benign according to our data. Variant chr6-10528886-A-C is described in ClinVar as Benign. ClinVar VariationId is 1285739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

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.-26A>C		5_prime_UTR	Exon 3 of 5	NP_663624.1	Q8N0V5-1
	GCNT2	NM_001374747.1		c.-26A>C		5_prime_UTR	Exon 1 of 3	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.-26A>C		5_prime_UTR	Exon 3 of 5	ENSP00000419411.2	Q8N0V5-1
	GCNT2	ENST00000379597.7	TSL:1	c.-26A>C		5_prime_UTR	Exon 1 of 3	ENSP00000368917.3	Q8N0V5-1
	GCNT2	ENST00000410107.5	TSL:1	c.67+19728A>C		intron	N/A	ENSP00000386321.1	B7ZBL3

Frequencies

GnomAD3 genomes AF: 0.0573 AC: 8724 AN: 152140 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.0789

GnomAD2 exomes AF: 0.0582 AC: 14605 AN: 251022 AF XY: 0.0594

Gnomad AFR exome AF: 0.0163

Gnomad AMR exome AF: 0.0464

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0361

Gnomad NFE exome AF: 0.0841

Gnomad OTH exome AF: 0.0731

GnomAD4 exome AF: 0.0757 AC: 105007 AN: 1387108 Hom.: 4679 Cov.: 24 AF XY: 0.0747 AC XY: 51891 AN XY: 694592

African (AFR) AF: 0.0125 AC: 401 AN: 32052

American (AMR) AF: 0.0490 AC: 2189 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 2999 AN: 25664

East Asian (EAS) AF: 0.000153 AC: 6 AN: 39324

South Asian (SAS) AF: 0.0237 AC: 2008 AN: 84790

European-Finnish (FIN) AF: 0.0367 AC: 1950 AN: 53188

Middle Eastern (MID) AF: 0.0873 AC: 447 AN: 5122

European-Non Finnish (NFE) AF: 0.0870 AC: 90814 AN: 1044394

Other (OTH) AF: 0.0724 AC: 4193 AN: 57936

GnomAD4 genome AF: 0.0573 AC: 8719 AN: 152258 Hom.: 370 Cov.: 32 AF XY: 0.0536 AC XY: 3988 AN XY: 74444

African (AFR) AF: 0.0175 AC: 727 AN: 41556

American (AMR) AF: 0.0684 AC: 1045 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4824

European-Finnish (FIN) AF: 0.0333 AC: 353 AN: 10610

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0852 AC: 5798 AN: 68016

Other (OTH) AF: 0.0781 AC: 165 AN: 2112

Alfa AF: 0.0452 Hom.: 112

Bravo AF: 0.0594

Asia WGS AF: 0.00866 AC: 33 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.50
PhyloP100		0.069
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs79945859; hg19: chr6-10529119; COSMIC: COSV65457025; COSMIC: COSV65457025;