Genetic Variant FUT2:p.Ala86Thr (chr19-48703212-G-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_000511.6(FUT2):c.256G>A(p.Ala86Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FUT2
NM_000511.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.32

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.942

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT2	NM_000511.6 link	c.256G>A	p.Ala86Thr	missense_variant	Exon 2 of 2	ENST00000425340.3	NP_000502.4	Q10981A8K2L2
FUT2	NM_001097638.3 link	c.256G>A	p.Ala86Thr	missense_variant	Exon 2 of 2		NP_001091107.1	Q10981A8K2L2
LOC105447645	NR_131188.1 link	n.637C>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.256G>A	p.Ala86Thr	missense_variant	Exon 2 of 2	1	NM_000511.6	ENSP00000387498.2		Q10981
FUT2	ENST00000522966.2 link	c.256G>A	p.Ala86Thr	missense_variant	Exon 2 of 2	2		ENSP00000430227.2		Q10981

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461168

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726846

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

85860

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111990

Other (OTH)

AF:

0.00

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 15, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.256G>A (p.A86T) alteration is located in exon 2 (coding exon 1) of the FUT2 gene. This alteration results from a G to A substitution at nucleotide position 256, causing the alanine (A) at amino acid position 86 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

.;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

.;.;D

M_CAP

Uncertain

0.086

MetaRNN

Pathogenic

0.94

D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.0

.;M;M

PhyloP100

4.3

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.38, 0.40

MutPred

0.81

Loss of catalytic residue at M88 (P = 0.0489);Loss of catalytic residue at M88 (P = 0.0489);Loss of catalytic residue at M88 (P = 0.0489);

MVP

0.99

MPC

0.72

ClinPred

0.99

GERP RS

4.3

Varity_R

0.81

gMVP

0.74

Mutation Taster

=55/45

polymorphism

(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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chr19-48703212-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over