rs12139970

Variant names:

• chr1-230270714-G-T
• rs12139970
• NM_004481.5:c.1441-3731G>T

Variant summary

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

The NM_004481.5(GALNT2):​c.1441-3731G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,180 control chromosomes in the GnomAD database, including 3,969 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 0.20 (3969 hom., cov: 33)
• Consequence: GALNT2 NM_004481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.501
• 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

LOC124904542 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.281 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.1441-3731G>T		intron	N/A	NP_004472.1	A0A1L7NY50
	GALNT2	NM_001291866.2		c.1327-3731G>T		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.1441-3731G>T		intron	N/A	ENSP00000355632.4	Q10471-1
	GALNT2	ENST00000935982.1		c.1465-3731G>T		intron	N/A	ENSP00000606041.1
	GALNT2	ENST00000950855.1		c.1441-3731G>T		intron	N/A	ENSP00000620914.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30877 AN: 152062 Hom.: 3966 Cov.: 33

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.0431

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.203 AC: 30891 AN: 152180 Hom.: 3969 Cov.: 33 AF XY: 0.205 AC XY: 15232 AN XY: 74398

African (AFR) AF: 0.0490 AC: 2034 AN: 41534

American (AMR) AF: 0.198 AC: 3025 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3472

East Asian (EAS) AF: 0.0432 AC: 224 AN: 5182

South Asian (SAS) AF: 0.273 AC: 1317 AN: 4820

European-Finnish (FIN) AF: 0.303 AC: 3204 AN: 10564

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19360 AN: 67996

Other (OTH) AF: 0.223 AC: 472 AN: 2116

Alfa AF: 0.258 Hom.: 6722

Bravo AF: 0.188

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.3
DANN	Benign	0.83
PhyloP100		0.50
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: rs12139970; hg19: chr1-230406460;