chr19-48703029-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000511.6(FUT2):c.73A>G(p.Ile25Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00694 in 1,613,032 control chromosomes in the GnomAD database, including 545 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 275 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 270 hom. )

Consequence

FUT2
NM_000511.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -2.47

Publications

11 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017546713).

BP6

Variant 19-48703029-A-G is Benign according to our data. Variant chr19-48703029-A-G is described in ClinVar as [Benign]. Clinvar id is 979159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT2	NM_000511.6 link	c.73A>G	p.Ile25Val	missense_variant	Exon 2 of 2	ENST00000425340.3	NP_000502.4	Q10981A8K2L2
FUT2	NM_001097638.3 link	c.73A>G	p.Ile25Val	missense_variant	Exon 2 of 2		NP_001091107.1	Q10981A8K2L2
LOC105447645	NR_131188.1 link	n.820T>C		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.73A>G	p.Ile25Val	missense_variant	Exon 2 of 2	1	NM_000511.6	ENSP00000387498.2		Q10981
FUT2	ENST00000522966.2 link	c.73A>G	p.Ile25Val	missense_variant	Exon 2 of 2	2		ENSP00000430227.2		Q10981

Frequencies

GnomAD3 genomes

AF:

0.0335

AC:

5083

AN:

151948

Hom.:

263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000842

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.0273

GnomAD2 exomes

AF:

0.00933

AC:

2341

AN:

250942

AF XY:

0.00689

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.00781

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000985

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00415

AC:

6059

AN:

1460968

Hom.:

270

Cov.:

AF XY:

0.00364

AC XY:

2645

AN XY:

726796

show subpopulations

African (AFR)

AF:

0.119

AC:

3991

AN:

33478

American (AMR)

AF:

0.00785

AC:

351

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00180

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39582

South Asian (SAS)

AF:

0.000605

AC:

AN:

85890

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53040

Middle Eastern (MID)

AF:

0.0208

AC:

120

AN:

5768

European-Non Finnish (NFE)

AF:

0.000792

AC:

881

AN:

1112002

Other (OTH)

AF:

0.0102

AC:

617

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

367

734

1101

1468

1835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0337

AC:

5129

AN:

152064

Hom.:

275

Cov.:

AF XY:

0.0320

AC XY:

2375

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.114

AC:

4733

AN:

41492

American (AMR)

AF:

0.0158

AC:

241

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.000843

AC:

AN:

4744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00121

AC:

AN:

68028

Other (OTH)

AF:

0.0270

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

226

453

679

906

1132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0150

Hom.:

263

Bravo

AF:

0.0390

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.119

AC:

523

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.0113

AC:

1369

Asia WGS

AF:

0.0100

AC:

AN:

3418

EpiCase

AF:

0.00136

EpiControl

AF:

0.00172

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fucosyltransferase 6 deficiency

Benign:1

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

The heterozygous p.Ile25Val variant in FUT2 has been identified in at least 1 individual from South Africa (PMID: 9760207). In vitro functional studies provide some evidence that the p.Ile25Val variant may not impact protein function (PMID: 9760207). However, these types of assays may not accurately represent biological function. This variant is classified as benign for fucosyltransferase deficiency because it has been identified in >10% of African chromosomes by ExAC (http://gnomad.broadinstitute.org/). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

0.070

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.0050

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.015

.;T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.53

.;.;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.85

.;L;L

PhyloP100

-2.5

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.30

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.36

T;T;T

Sift4G

Benign

0.76

T;T;T

Polyphen

0.0090

.;B;B

Vest4

0.033, 0.020

MPC

0.15

ClinPred

0.010

GERP RS

-6.4

Varity_R

0.023

gMVP

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr19-48703029-A-G

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