Variant 19-48703368-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000511.6(FUT2):c.412C>T(p.Arg138Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00877 in 1,613,062 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as confers sensitivity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R138H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0066 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 71 hom. )

Consequence

FUT2
NM_000511.6 missense

Scores

Clinical Significance

confers sensitivity no assertion criteria provided O:1

Conservation

PhyloP100: 0.560

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014655948).

BS2

High Homozygotes in GnomAd at 6 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FUT2	NM_000511.6 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	2/2	ENST00000425340.3
LOC105447645	NR_131188.1 linkuse as main transcript	n.481G>A		non_coding_transcript_exon_variant	1/1
FUT2	NM_001097638.3 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT2	ENST00000425340.3 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	2/2	1	NM_000511.6	P1
FUT2	ENST00000522966.2 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	2/2	2		P1

Frequencies

GnomAD3 genomes

AF:

0.00661

AC:

1005

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00734

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000631

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00619

AC:

1549

AN:

250440

Hom.:

AF XY:

0.00625

AC XY:

848

AN XY:

135628

show subpopulations

Gnomad AFR exome

AF:

0.00143

Gnomad AMR exome

AF:

0.00492

Gnomad ASJ exome

AF:

0.00725

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000461

Gnomad FIN exome

AF:

0.00536

Gnomad NFE exome

AF:

0.00984

Gnomad OTH exome

AF:

0.00620

GnomAD4 exome

AF:

0.00899

AC:

13138

AN:

1460876

Hom.:

Cov.:

AF XY:

0.00862

AC XY:

6264

AN XY:

726698

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.00517

Gnomad4 ASJ exome

AF:

0.00719

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000664

Gnomad4 FIN exome

AF:

0.00578

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00701

GnomAD4 genome

AF:

0.00660

AC:

1004

AN:

152186

Hom.:

Cov.:

AF XY:

0.00618

AC XY:

460

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00733

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000632

Gnomad4 FIN

AF:

0.00584

Gnomad4 NFE

AF:

0.0102

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00864

Hom.:

Bravo

AF:

0.00644

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0104

AC:

ExAC

AF:

0.00617

AC:

748

EpiCase

AF:

0.0101

EpiControl

AF:

0.0110

ClinVar

Significance: confers sensitivity

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Familial Otitis Media

Other:1

confers sensitivity, no assertion criteria provided

research

University of Washington Center for Mendelian Genomics, University of Washington

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.060

Cadd

Uncertain

Dann

Pathogenic

1.0

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.66

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Pathogenic

0.88

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-4.3

D;D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.59, 0.85

MVP

0.96

MPC

0.85

ClinPred

0.033

GERP RS

4.8

Varity_R

0.44

gMVP

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over