rs1800028

Variant names:

• chr19-48703560-C-T
• rs1800028
• NM_000511.6:c.604C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-48703560-C-T
• chr19-48703560-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP5 BS2_Supporting

The NM_000511.6(FUT2):​c.604C>T​(p.Arg202*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00036 in 1,613,288 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00051 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (21 hom.)
• Consequence: FUT2 NM_000511.6 stop_gained
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1 U:1 O:1
• Conservation: PhyloP100: 0.351
• Publications: 24 publications found

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: Uncertain_significance. The variant received 0 ACMG points.

• PP5: Variant 19-48703560-C-T is Pathogenic according to our data. Variant chr19-48703560-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 225366.
• BS2: High Homozygotes in GnomAdExome4 at 21 BG geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT2	NM_000511.6	MANE Select	c.604C>T	p.Arg202*	stop_gained	Exon 2 of 2	NP_000502.4	A8K2L2
	FUT2	NM_001097638.3		c.604C>T	p.Arg202*	stop_gained	Exon 2 of 2	NP_001091107.1	Q10981
	LOC105447645	NR_131188.1		n.289G>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT2	ENST00000425340.3	TSL:1 MANE Select	c.604C>T	p.Arg202*	stop_gained	Exon 2 of 2	ENSP00000387498.2	Q10981
	FUT2	ENST00000522966.2	TSL:2	c.604C>T	p.Arg202*	stop_gained	Exon 2 of 2	ENSP00000430227.2	Q10981
	FUT2	ENST00000960751.1		c.604C>T	p.Arg202*	stop_gained	Exon 3 of 3	ENSP00000630810.1

Frequencies

GnomAD3 genomes AF: 0.000507 AC: 77 AN: 151992 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000525

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00712

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.000558 AC: 140 AN: 250894 AF XY: 0.000442

Gnomad AFR exome AF: 0.000617

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00576

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000345 AC: 504 AN: 1461180 Hom.: 21 Cov.: 80 AF XY: 0.000323 AC XY: 235 AN XY: 726844

African (AFR) AF: 0.000358 AC: 12 AN: 33480

American (AMR) AF: 0.000313 AC: 14 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00436 AC: 173 AN: 39700

South Asian (SAS) AF: 0.0000582 AC: 5 AN: 85892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000450 AC: 50 AN: 1112000

Other (OTH) AF: 0.00414 AC: 250 AN: 60348

GnomAD4 genome AF: 0.000506 AC: 77 AN: 152108 Hom.: 1 Cov.: 32 AF XY: 0.000484 AC XY: 36 AN XY: 74366

African (AFR) AF: 0.000554 AC: 23 AN: 41538

American (AMR) AF: 0.000524 AC: 8 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00713 AC: 37 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67988

Other (OTH) AF: 0.00332 AC: 7 AN: 2106

Alfa AF: 0.000746 Hom.: 17

Bravo AF: 0.000650

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000552 AC: 67

Asia WGS AF: 0.0170 AC: 58 AN: 3416

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Bombay phenotype (1)
1	-	-	VITAMIN B12 PLASMA LEVEL QUANTITATIVE TRAIT LOCUS 1 (1)
-	-	-	Familial Otitis Media (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.58	D
PhyloP100		0.35
Vest4		0.89
GERP RS		4.0
Mutation Taster		=94/106	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs1800028; hg19: chr19-49206817;