1-230067417-C-T

Variant names:

• chr1-230067417-C-T
• rs549065079
• NM_004481.5:c.126+11C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_004481.5(GALNT2):​c.126+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000317 in 1,135,896 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: GALNT2 NM_004481.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.195
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 1-230067417-C-T is Benign according to our data. Variant chr1-230067417-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3627717.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000179 (27/150962) while in subpopulation AMR AF = 0.000659 (10/15184). AF 95% confidence interval is 0.000357. There are 1 homozygotes in GnomAd4. There are 15 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT2	NM_004481.5	c.126+11C>T		intron_variant	Intron 1 of 15	ENST00000366672.5	NP_004472.1
GALNT2	NM_001291866.2	c.12+9339C>T		intron_variant	Intron 1 of 15		NP_001278795.1
GALNT2	NR_120373.2	n.169+11C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT2	ENST00000366672.5	c.126+11C>T		intron_variant	Intron 1 of 15	1	NM_004481.5	ENSP00000355632.4
GALNT2	ENST00000488903.1	n.148+11C>T		intron_variant	Intron 1 of 1	2
GALNT2	ENST00000494106.1	n.89+9339C>T		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.000179 AC: 27 AN: 150854 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000412

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 4474 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000914 AC: 9 AN: 984934 Hom.: 0 Cov.: 15 AF XY: 0.00000634 AC XY: 3 AN XY: 473206

African (AFR) AF: 0.000154 AC: 3 AN: 19516

American (AMR) AF: 0.000590 AC: 4 AN: 6778

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11588

East Asian (EAS) AF: 0.00 AC: 0 AN: 21852

South Asian (SAS) AF: 0.00 AC: 0 AN: 22756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 834730

Other (OTH) AF: 0.0000525 AC: 2 AN: 38090

GnomAD4 genome AF: 0.000179 AC: 27 AN: 150962 Hom.: 1 Cov.: 32 AF XY: 0.000203 AC XY: 15 AN XY: 73776

African (AFR) AF: 0.000411 AC: 17 AN: 41374

American (AMR) AF: 0.000659 AC: 10 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67598

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000212

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.97
PhyloP100		-0.20
PromoterAI		-0.025	Neutral

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: rs549065079; hg19: chr1-230203164;