1-230169242-A-G

Variant names:

• chr1-230169242-A-G
• rs10489615
• NM_004481.5:c.127-8976A>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.127-8976A>G 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 152,048 control chromosomes in the GnomAD database, including 20,629 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 (20629 hom., cov: 32)
• Consequence: GALNT2 NM_004481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 43 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.609 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT2	NM_004481.5	MANE Select	c.127-8976A>G		intron	N/A	NP_004472.1
	GALNT2	NM_001291866.2		c.13-8976A>G		intron	N/A	NP_001278795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT2	ENST00000366672.5	TSL:1 MANE Select	c.127-8976A>G		intron	N/A	ENSP00000355632.4
	GALNT2	ENST00000494106.1	TSL:5	n.90-8976A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76440 AN: 151930 Hom.: 20620 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.571

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.503 AC: 76460 AN: 152048 Hom.: 20629 Cov.: 32 AF XY: 0.498 AC XY: 37011 AN XY: 74322

African (AFR) AF: 0.302 AC: 12509 AN: 41484

American (AMR) AF: 0.577 AC: 8817 AN: 15278

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

East Asian (EAS) AF: 0.252 AC: 1303 AN: 5166

South Asian (SAS) AF: 0.433 AC: 2088 AN: 4818

European-Finnish (FIN) AF: 0.559 AC: 5893 AN: 10546

Middle Eastern (MID) AF: 0.569 AC: 165 AN: 290

European-Non Finnish (NFE) AF: 0.614 AC: 41761 AN: 67974

Other (OTH) AF: 0.542 AC: 1146 AN: 2114

Alfa AF: 0.573 Hom.: 110422

Bravo AF: 0.497

Asia WGS AF: 0.357 AC: 1237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.71
PhyloP100		-0.67
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: rs10489615; hg19: chr1-230304988; COSMIC: COSV107467368;