Genetic Variant FUT2:p.Ala104Val (chr19-48703267-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_000511.6(FUT2):c.311C>T(p.Ala104Val) variant causes a missense change. The variant allele was found at a frequency of 0.00187 in 1,613,000 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as confers sensitivity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 112 hom. )

Consequence

FUT2
NM_000511.6 missense

Scores

Clinical Significance

confers sensitivity no assertion criteria provided O:1

Conservation

PhyloP100: 4.73

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01712045).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0013 (198/152208) while in subpopulation SAS AF = 0.0194 (92/4738). AF 95% confidence interval is 0.0162. There are 3 homozygotes in GnomAd4. There are 101 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 3 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT2	NM_000511.6 link	c.311C>T	p.Ala104Val	missense_variant	Exon 2 of 2	ENST00000425340.3	NP_000502.4	Q10981A8K2L2
FUT2	NM_001097638.3 link	c.311C>T	p.Ala104Val	missense_variant	Exon 2 of 2		NP_001091107.1	Q10981A8K2L2
LOC105447645	NR_131188.1 link	n.582G>A		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.311C>T	p.Ala104Val	missense_variant	Exon 2 of 2	1	NM_000511.6	ENSP00000387498.2		Q10981
FUT2	ENST00000522966.2 link	c.311C>T	p.Ala104Val	missense_variant	Exon 2 of 2	2		ENSP00000430227.2		Q10981

Frequencies

GnomAD3 genomes

AF:

0.00130

AC:

198

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0194

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000955

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00352

AC:

872

AN:

247802

AF XY:

0.00444

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00300

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.00132

Gnomad OTH exome

AF:

0.00348

GnomAD4 exome

AF:

0.00193

AC:

2820

AN:

1460792

Hom.:

112

Cov.:

AF XY:

0.00254

AC XY:

1845

AN XY:

726648

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33480

American (AMR)

AF:

0.00101

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00276

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39696

South Asian (SAS)

AF:

0.0206

AC:

1770

AN:

85848

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52842

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000634

AC:

705

AN:

1111978

Other (OTH)

AF:

0.00252

AC:

152

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

233

466

699

932

1165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00130

AC:

198

AN:

152208

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41564

American (AMR)

AF:

0.00111

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.0194

AC:

AN:

4738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000955

AC:

AN:

68030

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.000812

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000933

AC:

ExAC

AF:

0.00386

AC:

468

EpiCase

AF:

0.00256

EpiControl

AF:

0.00308

ClinVar

Significance: confers sensitivity

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

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

0.31

BayesDel_addAF

Uncertain

0.055

BayesDel_noAF

Pathogenic

0.27

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

.;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

.;.;D

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.0

.;M;M

PhyloP100

4.7

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.2

D;D;D

REVEL

Pathogenic

0.78

Sift

Benign

0.039

D;T;T

Sift4G

Uncertain

0.019

D;T;T

Polyphen

1.0

.;D;D

Vest4

0.56, 0.82

MVP

0.98

MPC

0.73

ClinPred

0.051

GERP RS

4.2

Varity_R

0.29

gMVP

0.44

Mutation Taster

=76/24

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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chr19-48703267-C-T

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