chr1-230128097-T-C

Variant names:

• chr1-230128097-T-C
• rs2144297
• NM_004481.5:c.127-50121T>C

Variant summary

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

The NM_004481.5(GALNT2):​c.127-50121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,796 control chromosomes in the GnomAD database, including 21,541 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 0.53 (21541 hom., cov: 31)
• Consequence: GALNT2 NM_004481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT2	NM_004481.5	MANE Select	c.127-50121T>C		intron	N/A	NP_004472.1	A0A1L7NY50
	GALNT2	NM_001291866.2		c.13-50121T>C		intron	N/A	NP_001278795.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT2	ENST00000366672.5	TSL:1 MANE Select	c.127-50121T>C		intron	N/A	ENSP00000355632.4	Q10471-1
	GALNT2	ENST00000935982.1		c.127-50121T>C		intron	N/A	ENSP00000606041.1
	GALNT2	ENST00000950855.1		c.127-50121T>C		intron	N/A	ENSP00000620914.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79790 AN: 151678 Hom.: 21511 Cov.: 31

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.526 AC: 79886 AN: 151796 Hom.: 21541 Cov.: 31 AF XY: 0.525 AC XY: 38916 AN XY: 74168

African (AFR) AF: 0.636 AC: 26298 AN: 41374

American (AMR) AF: 0.507 AC: 7733 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1795 AN: 3472

East Asian (EAS) AF: 0.659 AC: 3384 AN: 5134

South Asian (SAS) AF: 0.482 AC: 2328 AN: 4826

European-Finnish (FIN) AF: 0.426 AC: 4482 AN: 10532

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32180 AN: 67882

Other (OTH) AF: 0.505 AC: 1065 AN: 2110

Alfa AF: 0.482 Hom.: 39270

Bravo AF: 0.538

Asia WGS AF: 0.583 AC: 2024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.46
PhyloP100		-1.6
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: rs2144297; hg19: chr1-230263844;