rs485186

chr19-48703949-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000511.6(FUT2):c.993A>G(p.Thr331=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,613,000 control chromosomes in the GnomAD database, including 200,381 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 0.46 (17310 hom., cov: 31)
  • Exomes 𝑓: 0.49 (183071 hom.)
• Consequence: FUT2 NM_000511.6 synonymous
• Clinical Significance: confers sensitivity no assertion criteria provided O:1
• Conservation: PhyloP100: -1.91

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP7: Synonymous conserved (PhyloP=-1.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUT2	NM_000511.6	c.993A>G	p.Thr331=	synonymous_variant	2/2	ENST00000425340.3
FUT2	NM_001097638.3	c.993A>G	p.Thr331=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT2	ENST00000425340.3	c.993A>G	p.Thr331=	synonymous_variant	2/2	1	NM_000511.6	P1
FUT2	ENST00000522966.2	c.993A>G	p.Thr331=	synonymous_variant	2/2	2		P1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70290 AN: 151822 Hom.: 17317 Cov.: 31

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.476

GnomAD3 exomes AF: 0.405 AC: 101715 AN: 250982 Hom.: 23971 AF XY: 0.409 AC XY: 55459 AN XY: 135680

Gnomad AFR exome AF: 0.508

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.476

Gnomad EAS exome AF: 0.00251

Gnomad SAS exome AF: 0.316

Gnomad FIN exome AF: 0.419

Gnomad NFE exome AF: 0.506

Gnomad OTH exome AF: 0.456

GnomAD4 exome AF: 0.486 AC: 710166 AN: 1461064 Hom.: 183071 Cov.: 58 AF XY: 0.481 AC XY: 349277 AN XY: 726778

Gnomad4 AFR exome AF: 0.511

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.472

Gnomad4 EAS exome AF: 0.00174

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.526

Gnomad4 OTH exome AF: 0.486

GnomAD4 genome AF: 0.463 AC: 70295 AN: 151936 Hom.: 17310 Cov.: 31 AF XY: 0.451 AC XY: 33469 AN XY: 74246

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.00387

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.470

Alfa AF: 0.494 Hom.: 31548

Bravo AF: 0.464

Asia WGS AF: 0.142 AC: 493 AN: 3416

EpiCase AF: 0.507

EpiControl AF: 0.510

ClinVar

Significance: confers sensitivity

Submissions summary: Other:1

Revision: no assertion criteria provided

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
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.27
Dann	Benign	0.39

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

Other links and lift over

dbSNP: rs485186; hg19: chr19-49207206; COSMIC: COSV67179318; COSMIC: COSV67179318;