NM_000511.6:c.10G>A

Variant names:

• chr19-48702966-G-A
• rs774871775
• NM_000511.6:c.10G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BS2_Supporting

The NM_000511.6(FUT2):​c.10G>A​(p.Val4Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,460,982 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000021 (2 hom.)
• Consequence: FUT2 NM_000511.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.45
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.069584996).
• BP6: Variant 19-48702966-G-A is Benign according to our data. Variant chr19-48702966-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2336717.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 BG geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.10G>A	p.Val4Ile	missense	Exon 2 of 2	NP_000502.4	A8K2L2
	FUT2	NM_001097638.3		c.10G>A	p.Val4Ile	missense	Exon 2 of 2	NP_001091107.1	Q10981
	LOC105447645	NR_131188.1		n.883C>T		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.10G>A	p.Val4Ile	missense	Exon 2 of 2	ENSP00000387498.2	Q10981
	FUT2	ENST00000522966.2	TSL:2	c.10G>A	p.Val4Ile	missense	Exon 2 of 2	ENSP00000430227.2	Q10981
	FUT2	ENST00000960751.1		c.10G>A	p.Val4Ile	missense	Exon 3 of 3	ENSP00000630810.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 250998 AF XY: 0.0000663

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1460982 Hom.: 2 Cov.: 36 AF XY: 0.0000344 AC XY: 25 AN XY: 726780

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39578

South Asian (SAS) AF: 0.000163 AC: 14 AN: 85876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1112000

Other (OTH) AF: 0.0000331 AC: 2 AN: 60346

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.012
DANN	Benign	0.87
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.070	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-2.5
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.22
Sift	Benign	0.30	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.059
MutPred		0.26		Gain of solvent accessibility (P = 0.0808)
MVP		0.65
MPC		0.15
ClinPred		0.061	T
GERP RS		-6.5
Varity_R		0.022
gMVP		0.10
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs774871775; hg19: chr19-49206223; COSMIC: COSV67179133;