rs56141211

chr6-10626447-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_145649.5(GCNT2):c.1049G>A(p.Gly350Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: GCNT2 NM_145649.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.22

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.904
• PP5: Variant 6-10626447-G-A is Pathogenic according to our data. Variant chr6-10626447-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 9128.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-10626447-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCNT2	NM_145649.5	c.1049G>A	p.Gly350Glu	missense_variant	5/5	ENST00000495262.7
GCNT2	NM_001491.3	c.1043G>A	p.Gly348Glu	missense_variant	3/3	ENST00000316170.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCNT2	ENST00000495262.7	c.1049G>A	p.Gly350Glu	missense_variant	5/5	2	NM_145649.5	P3
GCNT2	ENST00000316170.9	c.1043G>A	p.Gly348Glu	missense_variant	3/3	1	NM_001491.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000477 AC: 12 AN: 251338 Hom.: 0 AF XY: 0.0000662 AC XY: 9 AN XY: 135852

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000652

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461386 Hom.: 0 Cov.: 29 AF XY: 0.0000220 AC XY: 16 AN XY: 727056

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000731

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000189

ExAC AF: 0.0000741 AC: 9

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Cataract 13 with adult I phenotype Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 15, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Pathogenic	0.33
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D;T;T;.;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.90	D;D;D;D;D
MetaSVM	Uncertain	0.46	D
MutationTaster	Benign	1.0	A;A;A;A;A
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-7.3	D;D;D;D;D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0060	D;.;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	D;P;P;.;.
Vest4		0.97
MutPred		0.85		.;Loss of catalytic residue at D353 (P = 0.1067);Loss of catalytic residue at D353 (P = 0.1067);.;Loss of catalytic residue at D353 (P = 0.1067);
MVP		0.87
MPC		0.064
ClinPred		0.94	D
GERP RS		5.6
Varity_R		0.96
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs56141211; hg19: chr6-10626680;