rs492602

Positions:

• chr19-48703160-A-G
• chr19-48703160-A-T

Variant summary

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

The NM_000511.6(FUT2):​c.204A>G​(p.Ala68Ala) 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 1,613,034 control chromosomes in the GnomAD database, including 179,898 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (15739 hom., cov: 32)
  • Exomes 𝑓: 0.46 (164159 hom.)
• Consequence: FUT2 NM_000511.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.88

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP7: Synonymous conserved (PhyloP=-4.88 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/exons	MANE	Protein	UniProt
FUT2	NM_000511.6	c.204A>G	p.Ala68Ala	synonymous_variant	2/2	ENST00000425340.3	NP_000502.4
FUT2	NM_001097638.3	c.204A>G	p.Ala68Ala	synonymous_variant	2/2		NP_001091107.1
LOC105447645	NR_131188.1	n.689T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUT2	ENST00000425340.3	c.204A>G	p.Ala68Ala	synonymous_variant	2/2	1	NM_000511.6	ENSP00000387498.2
FUT2	ENST00000522966.2	c.204A>G	p.Ala68Ala	synonymous_variant	2/2	2		ENSP00000430227.2

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67006 AN: 151824 Hom.: 15746 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.00409

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.459

GnomAD3 exomes AF: 0.383 AC: 95977 AN: 250706 Hom.: 21415 AF XY: 0.387 AC XY: 52430 AN XY: 135538

Gnomad AFR exome AF: 0.498

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.00268

Gnomad SAS exome AF: 0.313

Gnomad FIN exome AF: 0.374

Gnomad NFE exome AF: 0.476

Gnomad OTH exome AF: 0.430

GnomAD4 exome AF: 0.460 AC: 671822 AN: 1461094 Hom.: 164159 Cov.: 65 AF XY: 0.455 AC XY: 330623 AN XY: 726808

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.276

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.00175

Gnomad4 SAS exome AF: 0.319

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.462

GnomAD4 genome AF: 0.441 AC: 67009 AN: 151940 Hom.: 15739 Cov.: 32 AF XY: 0.429 AC XY: 31852 AN XY: 74228

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.00410

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.453

Alfa AF: 0.454 Hom.: 32844

Bravo AF: 0.444

Asia WGS AF: 0.141 AC: 488 AN: 3420

EpiCase AF: 0.479

EpiControl AF: 0.480

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.25

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: rs492602; hg19: chr19-49206417; COSMIC: COSV67179303;