chr2-241776969-T-A

Variant names:

• chr2-241776969-T-A
• rs200875314
• NM_022134.3:c.14T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_022134.3(GAL3ST2):​c.14T>A​(p.Leu5Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,552,302 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (1 hom.)
• Consequence: GAL3ST2 NM_022134.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.24
• Publications: 2 publications found

Genes affected

GAL3ST2 (HGNC:24869): (galactose-3-O-sulfotransferase 2) This gene encodes a member of the galactose-3-O-sulfotransferase protein family. The product of this gene catalyzes sulfonation by transferring a sulfate group to the hydroxyl at C-3 of nonreducing beta-galactosyl residues, and it can act on both type 1 and type 2 (Galbeta 1-3/1-4GlcNAc-R) oligosaccharides with similar efficiencies, and on core 1 glycans. This enzyme has been implicated in tumor metastasis processes. This gene is different from the GAL3ST3 gene located on chromosome 11, which has also been referred to as GAL3ST2 and encodes a related enzyme with distinct tissue distribution and substrate specificities, compared to galactose-3-O-sulfotransferase 2. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.097926706).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022134.3. 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
	GAL3ST2	NM_022134.3	MANE Select	c.14T>A	p.Leu5Gln	missense	Exon 1 of 4	NP_071417.2	Q9H3Q3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL3ST2	ENST00000192314.7	TSL:1 MANE Select	c.14T>A	p.Leu5Gln	missense	Exon 1 of 4	ENSP00000192314.6	Q9H3Q3

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

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: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000102 AC: 22 AN: 216144 AF XY: 0.0000928

Gnomad AFR exome AF: 0.0000768

Gnomad AMR exome AF: 0.000103

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000170

Gnomad OTH exome AF: 0.000200

GnomAD4 exome AF: 0.000192 AC: 269 AN: 1399956 Hom.: 1 Cov.: 31 AF XY: 0.000179 AC XY: 124 AN XY: 694532

African (AFR) AF: 0.0000980 AC: 3 AN: 30608

American (AMR) AF: 0.0000997 AC: 4 AN: 40108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24386

East Asian (EAS) AF: 0.00 AC: 0 AN: 35048

South Asian (SAS) AF: 0.00 AC: 0 AN: 78712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5528

European-Non Finnish (NFE) AF: 0.000230 AC: 248 AN: 1076872

Other (OTH) AF: 0.000245 AC: 14 AN: 57202

GnomAD4 genome AF: 0.0000656 AC: 10 AN: 152346 Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2 AN XY: 74502

African (AFR) AF: 0.0000481 AC: 2 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000159 Hom.: 0

Bravo AF: 0.0000604

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000989 AC: 12

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	10
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.0066	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		-1.2
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.16
Sift	Uncertain	0.016	D
Sift4G	Benign	0.12	T
Polyphen		0.96	D
Vest4		0.15
MVP		0.040
MPC		1.0
ClinPred		0.53	D
GERP RS		-0.80
PromoterAI		-0.025	Neutral
Varity_R		0.20
gMVP		0.41
Mutation Taster		=96/4	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: rs200875314; hg19: chr2-242716384; COSMIC: COSV51951295;