NM_004481.5:c.220+10010T>G

Variant names:

• chr1-230188321-T-G
• rs611229
• NM_004481.5:c.220+10010T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004481.5(GALNT2):​c.220+10010T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,904 control chromosomes in the GnomAD database, including 18,135 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 0.47 (18135 hom., cov: 31)
• Consequence: GALNT2 NM_004481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 9 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT2	NM_004481.5	c.220+10010T>G		intron_variant	Intron 2 of 15	ENST00000366672.5	NP_004472.1
GALNT2	NM_001291866.2	c.106+10010T>G		intron_variant	Intron 2 of 15		NP_001278795.1
GALNT2	XM_017000964.3	c.127+10010T>G		intron_variant	Intron 3 of 16		XP_016856453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT2	ENST00000366672.5	c.220+10010T>G		intron_variant	Intron 2 of 15	1	NM_004481.5	ENSP00000355632.4
GALNT2	ENST00000494106.1	n.183+10010T>G		intron_variant	Intron 2 of 6	5

Frequencies

GnomAD3 genomes AF: 0.468 AC: 70965 AN: 151786 Hom.: 18104 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.468 AC: 71045 AN: 151904 Hom.: 18135 Cov.: 31 AF XY: 0.472 AC XY: 35014 AN XY: 74250

African (AFR) AF: 0.668 AC: 27655 AN: 41400

American (AMR) AF: 0.415 AC: 6337 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1268 AN: 3468

East Asian (EAS) AF: 0.706 AC: 3651 AN: 5172

South Asian (SAS) AF: 0.516 AC: 2481 AN: 4806

European-Finnish (FIN) AF: 0.410 AC: 4317 AN: 10536

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 24020 AN: 67950

Other (OTH) AF: 0.436 AC: 916 AN: 2100

Alfa AF: 0.395 Hom.: 50098

Bravo AF: 0.477

Asia WGS AF: 0.614 AC: 2134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.68
DANN	Benign	0.64
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs611229; hg19: chr1-230324067;