rs281377

Positions:

• chr19-48703346-C-G
• chr19-48703346-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000511.6(FUT2):​c.390C>G​(p.Asn130Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N130N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FUT2 NM_000511.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUT2	NM_000511.6	c.390C>G	p.Asn130Lys	missense_variant	2/2	ENST00000425340.3
LOC105447645	NR_131188.1	n.503G>C		non_coding_transcript_exon_variant	1/1
FUT2	NM_001097638.3	c.390C>G	p.Asn130Lys	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT2	ENST00000425340.3	c.390C>G	p.Asn130Lys	missense_variant	2/2	1	NM_000511.6	P1
FUT2	ENST00000522966.2	c.390C>G	p.Asn130Lys	missense_variant	2/2	2		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 86

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	.;T;T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.73	.;.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Uncertain	2.8	.;M;M
MutationTaster	Benign	0.89	P;P
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.021	D;T;T
Sift4G	Benign	0.12	T;T;T
Polyphen		0.89	.;P;P
Vest4		0.29, 0.43
MutPred		0.59		Gain of ubiquitination at N130 (P = 0.0219);Gain of ubiquitination at N130 (P = 0.0219);Gain of ubiquitination at N130 (P = 0.0219);
MVP		0.91
MPC		0.75
ClinPred		0.93	D
GERP RS		1.4
Varity_R		0.29
gMVP		0.30

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: rs281377; hg19: chr19-49206603;