chr19-48703029-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 16/21 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
• Publications: 11 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 -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 VariationId 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.

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.73A>G	p.Ile25Val	missense	Exon 2 of 2	NP_000502.4	A8K2L2
	FUT2	NM_001097638.3		c.73A>G	p.Ile25Val	missense	Exon 2 of 2	NP_001091107.1	Q10981
	LOC105447645	NR_131188.1		n.820T>C		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.73A>G	p.Ile25Val	missense	Exon 2 of 2	ENSP00000387498.2	Q10981
	FUT2	ENST00000522966.2	TSL:2	c.73A>G	p.Ile25Val	missense	Exon 2 of 2	ENSP00000430227.2	Q10981
	FUT2	ENST00000960751.1		c.73A>G	p.Ile25Val	missense	Exon 3 of 3	ENSP00000630810.1

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

GnomAD2 exomes AF: 0.00933 AC: 2341 AN: 250942 AF XY: 0.00689

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 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

African (AFR) AF: 0.119 AC: 3991 AN: 33478

American (AMR) AF: 0.00785 AC: 351 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 47 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.000605 AC: 52 AN: 85890

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53040

Middle Eastern (MID) AF: 0.0208 AC: 120 AN: 5768

European-Non Finnish (NFE) AF: 0.000792 AC: 881 AN: 1112002

Other (OTH) AF: 0.0102 AC: 617 AN: 60348

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

African (AFR) AF: 0.114 AC: 4733 AN: 41492

American (AMR) AF: 0.0158 AC: 241 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.000843 AC: 4 AN: 4744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

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

European-Non Finnish (NFE) AF: 0.00121 AC: 82 AN: 68028

Other (OTH) AF: 0.0270 AC: 57 AN: 2110

Alfa AF: 0.0150 Hom.: 263

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Fucosyltransferase 6 deficiency (1)
-	-	1	not provided (1)
-	-	-	Familial Otitis Media (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.85	L
PhyloP100		-2.5
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.17
Sift	Benign	0.36	T
Sift4G	Benign	0.76	T
Polyphen		0.0090	B
Vest4		0.033
MPC		0.15
ClinPred		0.010	T
GERP RS		-6.4
Varity_R		0.023
gMVP		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1800021; hg19: chr19-49206286;