Genetic Variant GALNT2:p.Gly33Arg (chr1-230067377-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004481.5(GALNT2):c.97G>A(p.Gly33Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GALNT2
NM_004481.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.77

Publications

0 publications found

Variant links:

Genes affected

GALNT2 (HGNC:4124): (polypeptide N-acetylgalactosaminyltransferase 2) This gene encodes a member of the glycosyltransferase 2 protein family. Members of this family initiate mucin-type O-glycoslation of peptides in the Golgi apparatus. The encoded protein may be involved in O-linked glycosylation of the immunoglobulin A1 hinge region. This gene may influence triglyceride levels, and may be involved Type 2 diabetes, as well as several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

GALNT2 Gene-Disease associations (from GenCC):

congenital disorder of glycosylation, type iit
Inheritance: AR Classification: STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

GALNT2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26545304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT2	NM_004481.5 link	c.97G>A	p.Gly33Arg	missense_variant	Exon 1 of 16	ENST00000366672.5	NP_004472.1	Q10471-1A0A1L7NY50
GALNT2	NR_120373.2 link	n.140G>A		non_coding_transcript_exon_variant	Exon 1 of 2
GALNT2	NM_001291866.2 link	c.12+9299G>A		intron_variant	Intron 1 of 15		NP_001278795.1	Q10471G3V1S6B7Z6K2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GALNT2	ENST00000366672.5 link	c.97G>A	p.Gly33Arg	missense_variant	Exon 1 of 16	1	NM_004481.5	ENSP00000355632.4	Q10471-1
GALNT2	ENST00000488903.1 link	n.119G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
GALNT2	ENST00000494106.1 link	n.89+9299G>A		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

52164

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1144022

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

557598

African (AFR)

AF:

0.00

AC:

AN:

22730

American (AMR)

AF:

0.00

AC:

AN:

11982

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15904

East Asian (EAS)

AF:

0.00

AC:

AN:

24348

South Asian (SAS)

AF:

0.00

AC:

AN:

38876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

947138

Other (OTH)

AF:

0.00

AC:

AN:

44038

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

GALNT2: PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

PhyloP100

3.8

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.25

REVEL

Benign

0.15

Sift

Benign

0.40

Sift4G

Benign

0.50

Polyphen

0.64

Vest4

0.27

MutPred

0.28

Gain of methylation at G33 (P = 0.0089);

MVP

0.62

MPC

0.65

ClinPred

0.43

GERP RS

2.9

PromoterAI

0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.071

gMVP

0.62

Mutation Taster

=80/20

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over