rs1997947

Variant names:

• chr1-230148017-G-A
• rs1997947
• NM_004481.5:c.127-30201G>A

Variant summary

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

The NM_004481.5(GALNT2):​c.127-30201G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,158 control chromosomes in the GnomAD database, including 46,065 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 0.77 (46065 hom., cov: 33)
• Consequence: GALNT2 NM_004481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT2	NM_004481.5	c.127-30201G>A		intron_variant	Intron 1 of 15	ENST00000366672.5	NP_004472.1
GALNT2	NM_001291866.2	c.13-30201G>A		intron_variant	Intron 1 of 15		NP_001278795.1
GALNT2	XM_017000964.3	c.34-30201G>A		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.127-30201G>A		intron_variant	Intron 1 of 15	1	NM_004481.5	ENSP00000355632.4
GALNT2	ENST00000494106.1	n.90-30201G>A		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117593 AN: 152038 Hom.: 46019 Cov.: 33

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.773 AC: 117693 AN: 152158 Hom.: 46065 Cov.: 33 AF XY: 0.768 AC XY: 57104 AN XY: 74370

African (AFR) AF: 0.775 AC: 32190 AN: 41516

American (AMR) AF: 0.805 AC: 12315 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2740 AN: 3470

East Asian (EAS) AF: 0.359 AC: 1846 AN: 5144

South Asian (SAS) AF: 0.763 AC: 3674 AN: 4818

European-Finnish (FIN) AF: 0.734 AC: 7770 AN: 10586

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54518 AN: 68000

Other (OTH) AF: 0.776 AC: 1641 AN: 2116

Alfa AF: 0.789 Hom.: 8362

Bravo AF: 0.774

Asia WGS AF: 0.597 AC: 2078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.42
DANN	Benign	0.76
PhyloP100		-2.8
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: rs1997947; hg19: chr1-230283764;