chr1-230169566-G-A

Variant names:

• chr1-230169566-G-A
• rs1321257
• NM_004481.5:c.127-8652G>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.127-8652G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,110 control chromosomes in the GnomAD database, including 20,639 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 0.50 (20639 hom., cov: 33)
• Consequence: GALNT2 NM_004481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 27 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT2	NM_004481.5	c.127-8652G>A		intron_variant	Intron 1 of 15	ENST00000366672.5	NP_004472.1
GALNT2	NM_001291866.2	c.13-8652G>A		intron_variant	Intron 1 of 15		NP_001278795.1
GALNT2	XM_017000964.3	c.34-8652G>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.127-8652G>A		intron_variant	Intron 1 of 15	1	NM_004481.5	ENSP00000355632.4
GALNT2	ENST00000494106.1	n.90-8652G>A		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76462 AN: 151992 Hom.: 20630 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.503 AC: 76482 AN: 152110 Hom.: 20639 Cov.: 33 AF XY: 0.498 AC XY: 37013 AN XY: 74356

African (AFR) AF: 0.302 AC: 12507 AN: 41476

American (AMR) AF: 0.577 AC: 8816 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2211 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1305 AN: 5184

South Asian (SAS) AF: 0.433 AC: 2090 AN: 4822

European-Finnish (FIN) AF: 0.557 AC: 5892 AN: 10574

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41779 AN: 68000

Other (OTH) AF: 0.543 AC: 1145 AN: 2108

Alfa AF: 0.558 Hom.: 36390

Bravo AF: 0.497

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		-0.18
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: rs1321257; hg19: chr1-230305312;