1-230215611-A-G

Position:

• chr1-230215611-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004481.5(GALNT2):​c.374+12321A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,108 control chromosomes in the GnomAD database, including 27,303 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 0.57 (27303 hom., cov: 33)
• Consequence: GALNT2 NM_004481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALNT2	NM_004481.5	c.374+12321A>G		intron_variant		ENST00000366672.5	NP_004472.1
GALNT2	NM_001291866.2	c.260+12321A>G		intron_variant			NP_001278795.1
GALNT2	XM_017000964.3	c.281+12321A>G		intron_variant			XP_016856453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT2	ENST00000366672.5	c.374+12321A>G		intron_variant		1	NM_004481.5	ENSP00000355632	P1
GALNT2	ENST00000494106.1	n.337+12321A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86419 AN: 151990 Hom.: 27262 Cov.: 33

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.569 AC: 86521 AN: 152108 Hom.: 27303 Cov.: 33 AF XY: 0.569 AC XY: 42336 AN XY: 74370

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.897

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.540

Alfa AF: 0.455 Hom.: 7753

Bravo AF: 0.600

Asia WGS AF: 0.688 AC: 2392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.5
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs910497; hg19: chr1-230351357;