GCNT2 p.Arg110Ser

Variant names:

• chr6-10556753-G-T
• NM_001491.3:c.330G>T
• GCNT2 p.Arg110Ser

Your query was ambiguous. Multiple possible variants found:

• chr6-10556753-G-T
• chr6-10556753-G-C
• chr6-10556751-AG-TC
• chr6-10556751-AGG-TCT
• chr6-10556751-AGG-TCC
• chr6-10556751-AGG-TCA

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001491.3(GCNT2):​c.330G>T​(p.Arg110Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R110R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GCNT2 NM_001491.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• 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, Labcorp Genetics (formerly Invitae), G2P
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.893

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>T	p.Arg110Ser	missense	Exon 1 of 3	NP_001482.1	Q8N0V5-2
	GCNT2	NM_145649.5	MANE Select	c.925+26917G>T		intron	N/A	NP_663624.1	Q8N0V5-1
	GCNT2	NM_001374747.1		c.925+26917G>T		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>T	p.Arg110Ser	missense	Exon 1 of 3	ENSP00000314844.3	Q8N0V5-2
	GCNT2	ENST00000495262.7	TSL:2 MANE Select	c.925+26917G>T		intron	N/A	ENSP00000419411.2	Q8N0V5-1
	GCNT2	ENST00000379597.7	TSL:1	c.925+26917G>T		intron	N/A	ENSP00000368917.3	Q8N0V5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	13
DANN	Uncertain	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.74	D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.97	T
PhyloP100		0.16
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.33
Sift4G	Uncertain	0.0020	D
Mutation Taster		=28/72	disease causing

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-10556986;