dbSNP rs602662: FUT2:p.Gly258Ser (chr19-48703728-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000511.6(FUT2):c.772G>A(p.Gly258Ser) variant causes a missense change. The variant allele was found at a frequency of 0.482 in 1,613,236 control chromosomes in the GnomAD database, including 199,138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as confers sensitivity,other (no stars).

Frequency

Genomes: 𝑓 0.46 ( 17061 hom., cov: 30)

Exomes 𝑓: 0.48 ( 182077 hom. )

Consequence

FUT2
NM_000511.6 missense

Scores

Clinical Significance

confers sensitivity; other no assertion criteria provided O:2

Conservation

PhyloP100: 4.26

Publications

194 publications found

Variant links:

Genes affected

FUT2 (HGNC:4013): (fucosyltransferase 2 (H blood group)) This gene is one of two encoding the galactoside 2-L-fucosyltransferase enzyme. The encoded protein is important for the final step in the soluble ABO blood group antigen synthesis pathway. It is also involved in cell-cell interaction, cell surface expression, and cell proliferation. Mutations in this gene are a cause of the H-Bombay blood group where red blood cells lack the H antigen. [provided by RefSeq, May 2022]

FUT2 links:

LOC105447645 (HGNC:):

LOC105447645 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010427326).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT2	NM_000511.6 link	c.772G>A	p.Gly258Ser	missense_variant	Exon 2 of 2	ENST00000425340.3	NP_000502.4	Q10981A8K2L2
FUT2	NM_001097638.3 link	c.772G>A	p.Gly258Ser	missense_variant	Exon 2 of 2		NP_001091107.1	Q10981A8K2L2
LOC105447645	NR_131188.1 link	n.121C>T		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT2	ENST00000425340.3 link	c.772G>A	p.Gly258Ser	missense_variant	Exon 2 of 2	1	NM_000511.6	ENSP00000387498.2		Q10981
FUT2	ENST00000522966.2 link	c.772G>A	p.Gly258Ser	missense_variant	Exon 2 of 2	2		ENSP00000430227.2		Q10981

Frequencies

GnomAD3 genomes

AF:

0.460

AC:

69785

AN:

151682

Hom.:

17068

Cov.:

show subpopulations

Gnomad AFR

AF:

0.503

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.00386

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.410

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.477

GnomAD2 exomes

AF:

0.404

AC:

101486

AN:

251166

AF XY:

0.408

show subpopulations

Gnomad AFR exome

AF:

0.501

Gnomad AMR exome

AF:

0.280

Gnomad ASJ exome

AF:

0.476

Gnomad EAS exome

AF:

0.00218

Gnomad FIN exome

AF:

0.417

Gnomad NFE exome

AF:

0.505

Gnomad OTH exome

AF:

0.454

GnomAD4 exome

AF:

0.485

AC:

708333

AN:

1461438

Hom.:

182077

Cov.:

AF XY:

0.479

AC XY:

348385

AN XY:

726970

show subpopulations

African (AFR)

AF:

0.505

AC:

16894

AN:

33480

American (AMR)

AF:

0.293

AC:

13089

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.472

AC:

12328

AN:

26136

East Asian (EAS)

AF:

0.00156

AC:

AN:

39674

South Asian (SAS)

AF:

0.322

AC:

27671

AN:

85890

European-Finnish (FIN)

AF:

0.419

AC:

22402

AN:

53416

Middle Eastern (MID)

AF:

0.540

AC:

3113

AN:

5768

European-Non Finnish (NFE)

AF:

0.525

AC:

583532

AN:

1112000

Other (OTH)

AF:

0.485

AC:

29242

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

24453

48906

73358

97811

122264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16484

32968

49452

65936

82420

<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:

0.460

AC:

69790

AN:

151798

Hom.:

17061

Cov.:

AF XY:

0.448

AC XY:

33209

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.502

AC:

20791

AN:

41396

American (AMR)

AF:

0.386

AC:

5886

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

1638

AN:

3466

East Asian (EAS)

AF:

0.00387

AC:

AN:

5168

South Asian (SAS)

AF:

0.293

AC:

1387

AN:

4726

European-Finnish (FIN)

AF:

0.410

AC:

4323

AN:

10550

Middle Eastern (MID)

AF:

0.589

AC:

172

AN:

292

European-Non Finnish (NFE)

AF:

0.504

AC:

34255

AN:

67928

Other (OTH)

AF:

0.471

AC:

994

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1834

3668

5501

7335

9169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<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:

0.484

Hom.:

62365

Bravo

AF:

0.461

TwinsUK

AF:

0.522

AC:

1934

ALSPAC

AF:

0.528

AC:

2036

ESP6500AA

AF:

0.502

AC:

2210

ESP6500EA

AF:

0.518

AC:

4457

ExAC

AF:

0.410

AC:

49741

Asia WGS

AF:

0.142

AC:

491

AN:

3416

EpiCase

AF:

0.506

EpiControl

AF:

0.508

ClinVar

Significance: confers sensitivity; other

Submissions summary: Other:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Levothyroxine response

Other:1

Pharmacogenomics/Precision medicine lab, University of Petra

Significance:other

Review Status:no assertion criteria provided

Collection Method:research

- The snp had no effect on levothyroxine dosage requirement nor thyroid hormone nor b12 levels in our study

Familial Otitis Media

Other:1

University of Washington Center for Mendelian Genomics, University of Washington

Significance:confers sensitivity

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

0.050

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.78

.;T

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-1.4

MutationAssessor

Pathogenic

3.0

M;M

PhyloP100

4.3

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-4.3

D;D

REVEL

Uncertain

0.44

Sift

Benign

0.068

T;T

Sift4G

Uncertain

0.049

D;D

Polyphen

1.0

D;D

Vest4

0.26

MPC

0.72

ClinPred

0.050

GERP RS

5.3

Varity_R

0.30

gMVP

0.54

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over