Genetic Variant GAL3ST2:c.29+1G>A (chr2-241776985-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_022134.3(GAL3ST2):c.29+1G>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00526 in 1,539,698 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0037 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 25 hom. )

Consequence

GAL3ST2
NM_022134.3 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.11

Publications

7 publications found

Variant links:

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]

GAL3ST2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP6

Variant 2-241776985-G-A is Benign according to our data. Variant chr2-241776985-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 218793.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

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.29+1G>A		splice_donor intron	N/A	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.29+1G>A		splice_donor intron	N/A	ENSP00000192314.6	Q9H3Q3

Frequencies

GnomAD3 genomes

AF:

0.00368

AC:

561

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00630

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00362

AC:

766

AN:

211546

AF XY:

0.00362

show subpopulations

Gnomad AFR exome

AF:

0.000933

Gnomad AMR exome

AF:

0.00280

Gnomad ASJ exome

AF:

0.00558

Gnomad EAS exome

AF:

0.0000767

Gnomad FIN exome

AF:

0.000244

Gnomad NFE exome

AF:

0.00604

Gnomad OTH exome

AF:

0.00495

GnomAD4 exome

AF:

0.00543

AC:

7533

AN:

1387328

Hom.:

Cov.:

AF XY:

0.00528

AC XY:

3631

AN XY:

687710

show subpopulations

African (AFR)

AF:

0.000861

AC:

AN:

30188

American (AMR)

AF:

0.00306

AC:

118

AN:

38580

Ashkenazi Jewish (ASJ)

AF:

0.00697

AC:

167

AN:

23970

East Asian (EAS)

AF:

0.0000289

AC:

AN:

34624

South Asian (SAS)

AF:

0.000247

AC:

AN:

77012

European-Finnish (FIN)

AF:

0.000957

AC:

AN:

51194

Middle Eastern (MID)

AF:

0.000365

AC:

AN:

5480

European-Non Finnish (NFE)

AF:

0.00641

AC:

6855

AN:

1069720

Other (OTH)

AF:

0.00523

AC:

296

AN:

56560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

361

722

1083

1444

1805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00368

AC:

561

AN:

152370

Hom.:

Cov.:

AF XY:

0.00325

AC XY:

242

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

41596

American (AMR)

AF:

0.00216

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00979

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000376

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00630

AC:

429

AN:

68042

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

129

161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00548

Hom.:

Bravo

AF:

0.00392

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00361

AC:

438

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Benign

0.97

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.56

PhyloP100

1.1

GERP RS

1.9

PromoterAI

-0.19

Neutral

(source)

Mutation Taster

=18/82

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.90

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.20

Position offset: 25

DS_DL_spliceai

0.99

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over