19-48703374-A-C

Variant names:

• chr19-48703374-A-C
• rs1047781
• NM_000511.6:c.418A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000511.6(FUT2):​c.418A>C​(p.Ile140Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I140F) 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: 2.16
• Publications: 106 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34353977).

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.418A>C	p.Ile140Leu	missense	Exon 2 of 2	NP_000502.4	A8K2L2
	FUT2	NM_001097638.3		c.418A>C	p.Ile140Leu	missense	Exon 2 of 2	NP_001091107.1	Q10981
	LOC105447645	NR_131188.1		n.475T>G		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.418A>C	p.Ile140Leu	missense	Exon 2 of 2	ENSP00000387498.2	Q10981
	FUT2	ENST00000522966.2	TSL:2	c.418A>C	p.Ile140Leu	missense	Exon 2 of 2	ENSP00000430227.2	Q10981
	FUT2	ENST00000960751.1		c.418A>C	p.Ile140Leu	missense	Exon 3 of 3	ENSP00000630810.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 76

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	0.46	D
MutationAssessor	Benign	1.9	L
PhyloP100		2.2
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.77	N
REVEL	Uncertain	0.48
Sift	Benign	0.47	T
Sift4G	Benign	0.23	T
Polyphen		0.017	B
Vest4		0.24
MutPred		0.51		Gain of disorder (P = 0.1129)
MVP		0.93
MPC		0.23
ClinPred		0.15	T
GERP RS		3.8
Varity_R		0.23
gMVP		0.40
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: rs1047781; hg19: chr19-49206631;