1-230067361-C-T

Variant names:

• chr1-230067361-C-T
• rs28404113
• NM_004481.5:c.81C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_004481.5(GALNT2):​c.81C>T​(p.Gly27Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,354,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: GALNT2 NM_004481.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.53
• Publications: 1 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 1-230067361-C-T is Benign according to our data. Variant chr1-230067361-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3624237.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.53 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT2	NM_004481.5	c.81C>T	p.Gly27Gly	synonymous_variant	Exon 1 of 16	ENST00000366672.5	NP_004472.1
GALNT2	NR_120373.2	n.124C>T		non_coding_transcript_exon_variant	Exon 1 of 2
GALNT2	NM_001291866.2	c.12+9283C>T		intron_variant	Intron 1 of 15		NP_001278795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT2	ENST00000366672.5	c.81C>T	p.Gly27Gly	synonymous_variant	Exon 1 of 16	1	NM_004481.5	ENSP00000355632.4
GALNT2	ENST00000488903.1	n.103C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2
GALNT2	ENST00000494106.1	n.89+9283C>T		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.0000200 AC: 3 AN: 150030 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000297

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000336 AC: 3 AN: 89322 AF XY: 0.0000579

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000178

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000527

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000149 AC: 18 AN: 1204076 Hom.: 0 Cov.: 30 AF XY: 0.0000186 AC XY: 11 AN XY: 592166

African (AFR) AF: 0.00 AC: 0 AN: 24186

American (AMR) AF: 0.00 AC: 0 AN: 19588

Ashkenazi Jewish (ASJ) AF: 0.0000543 AC: 1 AN: 18406

East Asian (EAS) AF: 0.00 AC: 0 AN: 25186

South Asian (SAS) AF: 0.00 AC: 0 AN: 51616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4226

European-Non Finnish (NFE) AF: 0.0000174 AC: 17 AN: 974654

Other (OTH) AF: 0.00 AC: 0 AN: 46610

GnomAD4 genome AF: 0.0000200 AC: 3 AN: 150030 Hom.: 0 Cov.: 32 AF XY: 0.0000273 AC XY: 2 AN XY: 73154

African (AFR) AF: 0.0000243 AC: 1 AN: 41112

American (AMR) AF: 0.00 AC: 0 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3426

East Asian (EAS) AF: 0.00 AC: 0 AN: 5090

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000297 AC: 2 AN: 67242

Other (OTH) AF: 0.00 AC: 0 AN: 2056

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	17
DANN	Benign	0.96
PhyloP100		1.5
PromoterAI		0.058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs28404113; hg19: chr1-230203108;