rs2144300

Variant names:

• chr1-230159169-C-T
• rs2144300
• NM_004481.5:c.127-19049C>T

Variant summary

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

The NM_004481.5(GALNT2):​c.127-19049C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,018 control chromosomes in the GnomAD database, including 18,154 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 (18154 hom., cov: 32)
• Consequence: GALNT2 NM_004481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 89 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT2	NM_004481.5	c.127-19049C>T		intron_variant	Intron 1 of 15	ENST00000366672.5	NP_004472.1
GALNT2	NM_001291866.2	c.13-19049C>T		intron_variant	Intron 1 of 15		NP_001278795.1
GALNT2	XM_017000964.3	c.34-19049C>T		intron_variant	Intron 2 of 16		XP_016856453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT2	ENST00000366672.5	c.127-19049C>T		intron_variant	Intron 1 of 15	1	NM_004481.5	ENSP00000355632.4
GALNT2	ENST00000494106.1	n.90-19049C>T		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67697 AN: 151900 Hom.: 18150 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.445 AC: 67710 AN: 152018 Hom.: 18154 Cov.: 32 AF XY: 0.442 AC XY: 32859 AN XY: 74304

African (AFR) AF: 0.137 AC: 5705 AN: 41492

American (AMR) AF: 0.546 AC: 8347 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2120 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1035 AN: 5162

South Asian (SAS) AF: 0.421 AC: 2033 AN: 4828

European-Finnish (FIN) AF: 0.538 AC: 5679 AN: 10548

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41009 AN: 67918

Other (OTH) AF: 0.503 AC: 1063 AN: 2114

Alfa AF: 0.546 Hom.: 95139

Bravo AF: 0.433

Asia WGS AF: 0.318 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.4
DANN	Benign	0.76
PhyloP100		-0.23
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: rs2144300; hg19: chr1-230294916;