Genetic Variant GALNT2:c.127-18274G>A (chr1-230159944-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004481.5(GALNT2):c.127-18274G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,022 control chromosomes in the GnomAD database, including 18,286 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 18286 hom., cov: 31)

Consequence

GALNT2
NM_004481.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.683

Publications

168 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
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
congenital disorder of glycosylation, type iit
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

GALNT2 links:

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new If you want to explore the variant's impact on the transcript NM_004481.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004481.5. 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
	GALNT2	NM_004481.5	MANE Select	c.127-18274G>A		intron	N/A	NP_004472.1	A0A1L7NY50
	GALNT2	NM_001291866.2		c.13-18274G>A		intron	N/A	NP_001278795.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GALNT2	ENST00000366672.5	TSL:1 MANE Select	c.127-18274G>A	intron	N/A	ENSP00000355632.4	Q10471-1
GALNT2	ENST00000935982.1		c.127-18274G>A	intron	N/A	ENSP00000606041.1
GALNT2	ENST00000950855.1		c.127-18274G>A	intron	N/A	ENSP00000620914.1

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

68019

AN:

151902

Hom.:

18279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.627

Gnomad AMR

AF:

0.554

Gnomad ASJ

AF:

0.610

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.510

Gnomad NFE

AF:

0.604

Gnomad OTH

AF:

0.502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.448

AC:

68034

AN:

152022

Hom.:

18286

Cov.:

AF XY:

0.444

AC XY:

33021

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.138

AC:

5716

AN:

41488

American (AMR)

AF:

0.554

AC:

8463

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

2115

AN:

3466

East Asian (EAS)

AF:

0.231

AC:

1190

AN:

5158

South Asian (SAS)

AF:

0.421

AC:

2022

AN:

4806

European-Finnish (FIN)

AF:

0.539

AC:

5705

AN:

10576

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.604

AC:

41040

AN:

67938

Other (OTH)

AF:

0.505

AC:

1066

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1626

3253

4879

6506

8132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

606

1212

1818

2424

3030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.550

Hom.:

92869

Bravo

AF:

0.436

Asia WGS

AF:

0.334

AC:

1158

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

0.68

Mutation Taster

=100/0

polymorphism (auto)

(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

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over