rs1800022

Variant names:

• chr19-48703368-C-T
• rs1800022
• NM_000511.6:c.412C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000511.6(FUT2):​c.412C>T​(p.Arg138Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00877 in 1,613,062 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as confers sensitivity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R138H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0066 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0090 (71 hom.)
• Consequence: FUT2 NM_000511.6 missense
• Clinical Significance: confers sensitivity no assertion criteria provided O:1
• Conservation: PhyloP100: 0.560
• Publications: 20 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014655948).
• BS2: High Homozygotes in GnomAd4 at 6 BG gene

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.412C>T	p.Arg138Cys	missense	Exon 2 of 2	NP_000502.4	A8K2L2
	FUT2	NM_001097638.3		c.412C>T	p.Arg138Cys	missense	Exon 2 of 2	NP_001091107.1	Q10981
	LOC105447645	NR_131188.1		n.481G>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.412C>T	p.Arg138Cys	missense	Exon 2 of 2	ENSP00000387498.2	Q10981
	FUT2	ENST00000522966.2	TSL:2	c.412C>T	p.Arg138Cys	missense	Exon 2 of 2	ENSP00000430227.2	Q10981
	FUT2	ENST00000960751.1		c.412C>T	p.Arg138Cys	missense	Exon 3 of 3	ENSP00000630810.1

Frequencies

GnomAD3 genomes AF: 0.00661 AC: 1005 AN: 152070 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00734

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000631

Gnomad FIN AF: 0.00584

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00619 AC: 1549 AN: 250440 AF XY: 0.00625

Gnomad AFR exome AF: 0.00143

Gnomad AMR exome AF: 0.00492

Gnomad ASJ exome AF: 0.00725

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00536

Gnomad NFE exome AF: 0.00984

Gnomad OTH exome AF: 0.00620

GnomAD4 exome AF: 0.00899 AC: 13138 AN: 1460876 Hom.: 71 Cov.: 77 AF XY: 0.00862 AC XY: 6264 AN XY: 726698

African (AFR) AF: 0.00137 AC: 46 AN: 33480

American (AMR) AF: 0.00517 AC: 231 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00719 AC: 188 AN: 26130

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.000664 AC: 57 AN: 85888

European-Finnish (FIN) AF: 0.00578 AC: 306 AN: 52908

Middle Eastern (MID) AF: 0.00468 AC: 27 AN: 5768

European-Non Finnish (NFE) AF: 0.0107 AC: 11856 AN: 1111944

Other (OTH) AF: 0.00701 AC: 423 AN: 60338

GnomAD4 genome AF: 0.00660 AC: 1004 AN: 152186 Hom.: 6 Cov.: 32 AF XY: 0.00618 AC XY: 460 AN XY: 74390

African (AFR) AF: 0.00200 AC: 83 AN: 41568

American (AMR) AF: 0.00733 AC: 112 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00951 AC: 33 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000632 AC: 3 AN: 4750

European-Finnish (FIN) AF: 0.00584 AC: 62 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0102 AC: 692 AN: 68018

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.00914 Hom.: 18

Bravo AF: 0.00644

TwinsUK AF: 0.00917 AC: 34

ALSPAC AF: 0.0114 AC: 44

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.0104 AC: 89

ExAC AF: 0.00617 AC: 748

EpiCase AF: 0.0101

EpiControl AF: 0.0110

ClinVar

ClinVar submissions as Germline

Significance: confers sensitivity

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Familial Otitis Media (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.015	T
MetaSVM	Pathogenic	0.88	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.56
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.59
MVP		0.96
MPC		0.85
ClinPred		0.033	T
GERP RS		4.8
Varity_R		0.44
gMVP		0.49
Mutation Taster		=85/15	polymorphism

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: rs1800022; hg19: chr19-49206625; COSMIC: COSV67179913;