chr1-230175226-T-C

Variant names:

• chr1-230175226-T-C
• rs1124110
• NM_004481.5:c.127-2992T>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.127-2992T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,228 control chromosomes in the GnomAD database, including 1,391 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 0.12 (1391 hom., cov: 32)
• Consequence: GALNT2 NM_004481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• 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: 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 (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT2	NM_004481.5	c.127-2992T>C		intron_variant	Intron 1 of 15	ENST00000366672.5	NP_004472.1
GALNT2	NM_001291866.2	c.13-2992T>C		intron_variant	Intron 1 of 15		NP_001278795.1
GALNT2	XM_017000964.3	c.34-2992T>C		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.127-2992T>C		intron_variant	Intron 1 of 15	1	NM_004481.5	ENSP00000355632.4
GALNT2	ENST00000494106.1	n.90-2992T>C		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18700 AN: 152110 Hom.: 1381 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0766

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0906

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.123 AC: 18733 AN: 152228 Hom.: 1391 Cov.: 32 AF XY: 0.126 AC XY: 9345 AN XY: 74446

African (AFR) AF: 0.148 AC: 6139 AN: 41522

American (AMR) AF: 0.178 AC: 2721 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 266 AN: 3472

East Asian (EAS) AF: 0.262 AC: 1355 AN: 5176

South Asian (SAS) AF: 0.190 AC: 918 AN: 4828

European-Finnish (FIN) AF: 0.0763 AC: 810 AN: 10614

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0906 AC: 6159 AN: 68008

Other (OTH) AF: 0.119 AC: 251 AN: 2110

Alfa AF: 0.108 Hom.: 1426

Bravo AF: 0.132

Asia WGS AF: 0.235 AC: 816 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	2.0
DANN	Benign	0.68
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1124110; hg19: chr1-230310972;