1-230175226-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GALNT2	NM_004481.5	c.127-2992T>C		intron_variant		ENST00000366672.5
GALNT2	NM_001291866.2	c.13-2992T>C		intron_variant
GALNT2	XM_017000964.3	c.34-2992T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT2	ENST00000366672.5	c.127-2992T>C		intron_variant		1	NM_004481.5	P1
GALNT2	ENST00000494106.1	n.90-2992T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.0766

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.0763

Gnomad4 NFE AF: 0.0906

Gnomad4 OTH AF: 0.119

Alfa AF: 0.104 Hom.: 886

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1124110; hg19: chr1-230310972;