1-230067394-C-T

Variant names:

• chr1-230067394-C-T
• rs750017736
• NM_004481.5:c.114C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS1

The NM_004481.5(GALNT2):​c.114C>T​(p.Gly38Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,254,740 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 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: GALNT2 NM_004481.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.61
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 1-230067394-C-T is Benign according to our data. Variant chr1-230067394-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2187390.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.61 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000109 (120/1103896) while in subpopulation AMR AF = 0.000219 (2/9152). AF 95% confidence interval is 0.000103. There are 0 homozygotes in GnomAdExome4. There are 64 alleles in the male GnomAdExome4 subpopulation. Median coverage is 24. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT2	NM_004481.5	c.114C>T	p.Gly38Gly	synonymous_variant	Exon 1 of 16	ENST00000366672.5	NP_004472.1
GALNT2	NR_120373.2	n.157C>T		non_coding_transcript_exon_variant	Exon 1 of 2
GALNT2	NM_001291866.2	c.12+9316C>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.114C>T	p.Gly38Gly	synonymous_variant	Exon 1 of 16	1	NM_004481.5	ENSP00000355632.4
GALNT2	ENST00000488903.1	n.136C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2
GALNT2	ENST00000494106.1	n.89+9316C>T		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.0000464 AC: 7 AN: 150736 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

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: 0.0000740

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000237 AC: 5 AN: 21086 AF XY: 0.000160

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00144

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000156

Gnomad NFE exome AF: 0.000279

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000109 AC: 120 AN: 1103896 Hom.: 0 Cov.: 24 AF XY: 0.000120 AC XY: 64 AN XY: 534330

African (AFR) AF: 0.0000457 AC: 1 AN: 21894

American (AMR) AF: 0.000219 AC: 2 AN: 9152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14038

East Asian (EAS) AF: 0.00 AC: 0 AN: 23522

South Asian (SAS) AF: 0.00 AC: 0 AN: 32070

European-Finnish (FIN) AF: 0.0000312 AC: 1 AN: 32016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3404

European-Non Finnish (NFE) AF: 0.000122 AC: 113 AN: 925306

Other (OTH) AF: 0.0000706 AC: 3 AN: 42494

GnomAD4 genome AF: 0.0000464 AC: 7 AN: 150844 Hom.: 0 Cov.: 32 AF XY: 0.0000679 AC XY: 5 AN XY: 73688

African (AFR) AF: 0.00 AC: 0 AN: 41378

American (AMR) AF: 0.000132 AC: 2 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10072

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

European-Non Finnish (NFE) AF: 0.0000740 AC: 5 AN: 67530

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000642

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 21, 2022

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	-0.39
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		1.6
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Mutation Taster		=100/0	polymorphism

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: rs750017736; hg19: chr1-230203141;