Genetic Variant NM_000511.6:c.249C>T (chr19-48703205-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000511.6(FUT2):c.249C>T(p.Tyr83Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,612,814 control chromosomes in the GnomAD database, including 180,000 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 0.44 ( 15745 hom., cov: 32)

Exomes 𝑓: 0.46 ( 164255 hom. )

Consequence

FUT2
NM_000511.6 synonymous

Scores

Clinical Significance

confers sensitivity no assertion criteria provided O:1

Conservation

PhyloP100: -2.90

Publications

64 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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP7

Synonymous conserved (PhyloP=-2.9 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000511.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FUT2	NM_000511.6	MANE Select	c.249C>T	p.Tyr83Tyr	synonymous	Exon 2 of 2	NP_000502.4	A8K2L2
FUT2	NM_001097638.3		c.249C>T	p.Tyr83Tyr	synonymous	Exon 2 of 2	NP_001091107.1	Q10981
LOC105447645	NR_131188.1		n.644G>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FUT2	ENST00000425340.3	TSL:1 MANE Select	c.249C>T	p.Tyr83Tyr	synonymous	Exon 2 of 2	ENSP00000387498.2	Q10981
FUT2	ENST00000522966.2	TSL:2	c.249C>T	p.Tyr83Tyr	synonymous	Exon 2 of 2	ENSP00000430227.2	Q10981
FUT2	ENST00000960751.1		c.249C>T	p.Tyr83Tyr	synonymous	Exon 3 of 3	ENSP00000630810.1

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67017

AN:

151770

Hom.:

15752

Cov.:

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.350

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.00369

Gnomad SAS

AF:

0.296

Gnomad FIN

AF:

0.368

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.477

Gnomad OTH

AF:

0.459

GnomAD2 exomes

AF:

0.383

AC:

95841

AN:

250036

AF XY:

0.387

show subpopulations

Gnomad AFR exome

AF:

0.499

Gnomad AMR exome

AF:

0.265

Gnomad ASJ exome

AF:

0.452

Gnomad EAS exome

AF:

0.00257

Gnomad FIN exome

AF:

0.375

Gnomad NFE exome

AF:

0.476

Gnomad OTH exome

AF:

0.431

GnomAD4 exome

AF:

0.460

AC:

671969

AN:

1460928

Hom.:

164255

Cov.:

AF XY:

0.455

AC XY:

330703

AN XY:

726712

show subpopulations

African (AFR)

AF:

0.500

AC:

16743

AN:

33478

American (AMR)

AF:

0.277

AC:

12368

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.446

AC:

11660

AN:

26134

East Asian (EAS)

AF:

0.00166

AC:

AN:

39642

South Asian (SAS)

AF:

0.320

AC:

27468

AN:

85852

European-Finnish (FIN)

AF:

0.376

AC:

20033

AN:

53222

Middle Eastern (MID)

AF:

0.515

AC:

2965

AN:

5762

European-Non Finnish (NFE)

AF:

0.497

AC:

552724

AN:

1111834

Other (OTH)

AF:

0.463

AC:

27942

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

23088

46175

69263

92350

115438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15924

31848

47772

63696

79620

<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:

0.441

AC:

67021

AN:

151886

Hom.:

15745

Cov.:

AF XY:

0.430

AC XY:

31857

AN XY:

74168

show subpopulations

African (AFR)

AF:

0.499

AC:

20669

AN:

41458

American (AMR)

AF:

0.368

AC:

5619

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

1539

AN:

3466

East Asian (EAS)

AF:

0.00370

AC:

AN:

5138

South Asian (SAS)

AF:

0.295

AC:

1397

AN:

4728

European-Finnish (FIN)

AF:

0.368

AC:

3890

AN:

10562

Middle Eastern (MID)

AF:

0.558

AC:

164

AN:

294

European-Non Finnish (NFE)

AF:

0.477

AC:

32449

AN:

67962

Other (OTH)

AF:

0.453

AC:

956

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1843

3686

5529

7372

9215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

596

1192

1788

2384

2980

<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:

0.458

Hom.:

26412

Bravo

AF:

0.445

Asia WGS

AF:

0.142

AC:

491

AN:

3420

EpiCase

AF:

0.479

EpiControl

AF:

0.481

ClinVar

ClinVar submissions

Significance:confers sensitivity

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial Otitis Media (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.12

(source)

DANN

Benign

0.36

PhyloP100

-2.9

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over