dbSNP rs200874437: GCNT2:p.Ala247Ala (chr6-10557164-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001491.3(GCNT2):c.741G>A(p.Ala247Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000578 in 1,548,304 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00039 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 18 hom. )

Consequence

GCNT2
NM_001491.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -6.17

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 6-10557164-G-A is Benign according to our data. Variant chr6-10557164-G-A is described in ClinVar as [Benign]. Clinvar id is 258158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.17 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000394 (60/152218) while in subpopulation SAS AF= 0.0098 (47/4798). AF 95% confidence interval is 0.00757. There are 1 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 18 BG,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCNT2	NM_001491.3 link	c.741G>A	p.Ala247Ala	synonymous_variant	Exon 1 of 3	ENST00000316170.9	NP_001482.1	Q8N0V5-2
GCNT2	NM_145649.5 link	c.925+27328G>A		intron_variant	Intron 3 of 4	ENST00000495262.7	NP_663624.1	Q8N0V5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCNT2	ENST00000316170.9 link	c.741G>A	p.Ala247Ala	synonymous_variant	Exon 1 of 3	1	NM_001491.3	ENSP00000314844.3		Q8N0V5-2
GCNT2	ENST00000495262.7 link	c.925+27328G>A		intron_variant	Intron 3 of 4	2	NM_145649.5	ENSP00000419411.2		Q8N0V5-1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00958

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00110

AC:

214

AN:

195154

Hom.:

AF XY:

0.00137

AC XY:

142

AN XY:

103520

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000412

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000192

Gnomad OTH exome

AF:

0.000881

GnomAD4 exome

AF:

0.000598

AC:

835

AN:

1396086

Hom.:

Cov.:

AF XY:

0.000872

AC XY:

600

AN XY:

688332

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000299

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0100

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000443

Gnomad4 OTH exome

AF:

0.000695

GnomAD4 genome

AF:

0.000394

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00980

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000257

Hom.:

Bravo

AF:

0.000106

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cataract 13 with adult I phenotype

Benign:1

Nov 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.0020

DANN

Benign

0.23

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over