19-48703205-C-T

Variant names:

• chr19-48703205-C-T
• rs681343
• NM_000511.6:c.249C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: confers sensitivity no assertion criteria provided O:1
• Conservation: PhyloP100: -2.90

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]

LOC105447645 (HGNC:):

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT2	NM_000511.6	c.249C>T	p.Tyr83Tyr	synonymous_variant	Exon 2 of 2	ENST00000425340.3	NP_000502.4
FUT2	NM_001097638.3	c.249C>T	p.Tyr83Tyr	synonymous_variant	Exon 2 of 2		NP_001091107.1
LOC105447645	NR_131188.1	n.644G>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	c.249C>T	p.Tyr83Tyr	synonymous_variant	Exon 2 of 2	1	NM_000511.6	ENSP00000387498.2
FUT2	ENST00000522966.2	c.249C>T	p.Tyr83Tyr	synonymous_variant	Exon 2 of 2	2		ENSP00000430227.2

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67017 AN: 151770 Hom.: 15752 Cov.: 32

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

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.: 69 AF XY: 0.455 AC XY: 330703 AN XY: 726712

Gnomad4 AFR exome AF: 0.500 AC: 16743 AN: 33478

Gnomad4 AMR exome AF: 0.277 AC: 12368 AN: 44672

Gnomad4 ASJ exome AF: 0.446 AC: 11660 AN: 26134

Gnomad4 EAS exome AF: 0.00166 AC: 66 AN: 39642

Gnomad4 SAS exome AF: 0.320 AC: 27468 AN: 85852

Gnomad4 FIN exome AF: 0.376 AC: 20033 AN: 53222

Gnomad4 NFE exome AF: 0.497 AC: 552724 AN: 1111834

Gnomad4 Remaining exome AF: 0.463 AC: 27942 AN: 60332

GnomAD4 genome AF: 0.441 AC: 67021 AN: 151886 Hom.: 15745 Cov.: 32 AF XY: 0.430 AC XY: 31857 AN XY: 74168

Gnomad4 AFR AF: 0.499 AC: 0.498553 AN: 0.498553

Gnomad4 AMR AF: 0.368 AC: 0.368362 AN: 0.368362

Gnomad4 ASJ AF: 0.444 AC: 0.444028 AN: 0.444028

Gnomad4 EAS AF: 0.00370 AC: 0.00369794 AN: 0.00369794

Gnomad4 SAS AF: 0.295 AC: 0.295474 AN: 0.295474

Gnomad4 FIN AF: 0.368 AC: 0.368301 AN: 0.368301

Gnomad4 NFE AF: 0.477 AC: 0.477458 AN: 0.477458

Gnomad4 OTH AF: 0.453 AC: 0.452652 AN: 0.452652

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

Significance: confers sensitivity

Submissions summary: Other:1

Revision: no assertion criteria provided

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
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.12
DANN	Benign	0.36
Mutation Taster		=100/0	polymorphism (auto)

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: rs681343; hg19: chr19-49206462; COSMIC: COSV67179224;