chr1-230067353-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004481.5(GALNT2):​c.73T>G​(p.Ser25Ala) 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 benign outcome for this variant. 14/21 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)

Consequence

GALNT2
NM_004481.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26304793).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GALNT2NM_004481.5 linkuse as main transcriptc.73T>G p.Ser25Ala missense_variant 1/16 ENST00000366672.5
GALNT2NM_001291866.2 linkuse as main transcriptc.12+9275T>G intron_variant
GALNT2NR_120373.2 linkuse as main transcriptn.116T>G non_coding_transcript_exon_variant 1/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GALNT2ENST00000366672.5 linkuse as main transcriptc.73T>G p.Ser25Ala missense_variant 1/161 NM_004481.5 P1Q10471-1
GALNT2ENST00000488903.1 linkuse as main transcriptn.95T>G non_coding_transcript_exon_variant 1/22
GALNT2ENST00000494106.1 linkuse as main transcriptn.89+9275T>G intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 23, 2021This sequence change replaces serine with alanine at codon 25 of the GALNT2 protein (p.Ser25Ala). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and alanine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with GALNT2-related conditions. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
23
DANN
Benign
0.88
DEOGEN2
Benign
0.020
T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.59
D
LIST_S2
Benign
0.36
T
M_CAP
Pathogenic
0.95
D
MetaRNN
Benign
0.26
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
0.73
D;D;D
PrimateAI
Pathogenic
0.93
D
PROVEAN
Benign
-0.60
N
REVEL
Benign
0.11
Sift
Benign
0.36
T
Sift4G
Benign
0.64
T
Polyphen
0.027
B
Vest4
0.25
MutPred
0.46
Loss of glycosylation at S25 (P = 0.0013);
MVP
0.52
MPC
0.45
ClinPred
0.15
T
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.11
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.17
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-230203100; API