NM_000511.6:c.73A>G

Variant names:

• chr19-48703029-A-G
• rs1800021
• NM_000511.6:c.73A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000511.6(FUT2):​c.73A>G​(p.Ile25Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00694 in 1,613,032 control chromosomes in the GnomAD database, including 545 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (275 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (270 hom.)
• Consequence: FUT2 NM_000511.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -2.47

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017546713).
• BP6: Variant 19-48703029-A-G is Benign according to our data. Variant chr19-48703029-A-G is described in ClinVar as [Benign]. Clinvar id is 979159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT2	NM_000511.6	c.73A>G	p.Ile25Val	missense_variant	Exon 2 of 2	ENST00000425340.3	NP_000502.4
FUT2	NM_001097638.3	c.73A>G	p.Ile25Val	missense_variant	Exon 2 of 2		NP_001091107.1
LOC105447645	NR_131188.1	n.820T>C		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.73A>G	p.Ile25Val	missense_variant	Exon 2 of 2	1	NM_000511.6	ENSP00000387498.2
FUT2	ENST00000522966.2	c.73A>G	p.Ile25Val	missense_variant	Exon 2 of 2	2		ENSP00000430227.2

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 5083 AN: 151948 Hom.: 263 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000842

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.0273

GnomAD3 exomes AF: 0.00933 AC: 2341 AN: 250942 Hom.: 114 AF XY: 0.00689 AC XY: 935 AN XY: 135672

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.00781

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000658

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000985

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.00415 AC: 6059 AN: 1460968 Hom.: 270 Cov.: 36 AF XY: 0.00364 AC XY: 2645 AN XY: 726796

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.00785

Gnomad4 ASJ exome AF: 0.00180

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000605

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000792

Gnomad4 OTH exome AF: 0.0102

GnomAD4 genome AF: 0.0337 AC: 5129 AN: 152064 Hom.: 275 Cov.: 33 AF XY: 0.0320 AC XY: 2375 AN XY: 74314

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000843

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00121

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.00748 Hom.: 75

Bravo AF: 0.0390

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.119 AC: 523

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.0113 AC: 1369

Asia WGS AF: 0.0100 AC: 35 AN: 3418

EpiCase AF: 0.00136

EpiControl AF: 0.00172

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fucosyltransferase 6 deficiency Benign:1

-

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

The heterozygous p.Ile25Val variant in FUT2 has been identified in at least 1 individual from South Africa (PMID: 9760207). In vitro functional studies provide some evidence that the p.Ile25Val variant may not impact protein function (PMID: 9760207). However, these types of assays may not accurately represent biological function. This variant is classified as benign for fucosyltransferase deficiency because it has been identified in >10% of African chromosomes by ExAC (http://gnomad.broadinstitute.org/). -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.0050
DANN	Benign	0.26
DEOGEN2	Benign	0.015	.;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.53	.;.;T
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.85	.;L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.30	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.36	T;T;T
Sift4G	Benign	0.76	T;T;T
Polyphen		0.0090	.;B;B
Vest4		0.033, 0.020
MPC		0.15
ClinPred		0.010	T
GERP RS		-6.4
Varity_R		0.023
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1800021; hg19: chr19-49206286;