NM_000511.6:c.993A>G

Variant names:

• chr19-48703949-A-G
• rs485186
• NM_000511.6:c.993A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000511.6(FUT2):​c.993A>G​(p.Thr331Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,613,000 control chromosomes in the GnomAD database, including 200,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as confers sensitivity (no stars).

• Frequency:
  • Genomes: 𝑓 0.46 (17310 hom., cov: 31)
  • Exomes 𝑓: 0.49 (183071 hom.)
• Consequence: FUT2 NM_000511.6 synonymous
• Clinical Significance: confers sensitivity no assertion criteria provided O:1
• Conservation: PhyloP100: -1.91
• Publications: 52 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP7: Synonymous conserved (PhyloP=-1.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 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.993A>G	p.Thr331Thr	synonymous	Exon 2 of 2	NP_000502.4	A8K2L2
	FUT2	NM_001097638.3		c.993A>G	p.Thr331Thr	synonymous	Exon 2 of 2	NP_001091107.1	Q10981
	LOC105447645	NR_131188.1		n.-101T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT2	ENST00000425340.3	TSL:1 MANE Select	c.993A>G	p.Thr331Thr	synonymous	Exon 2 of 2	ENSP00000387498.2	Q10981
	FUT2	ENST00000522966.2	TSL:2	c.993A>G	p.Thr331Thr	synonymous	Exon 2 of 2	ENSP00000430227.2	Q10981
	FUT2	ENST00000960751.1		c.993A>G	p.Thr331Thr	synonymous	Exon 3 of 3	ENSP00000630810.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70290 AN: 151822 Hom.: 17317 Cov.: 31

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.476

GnomAD2 exomes AF: 0.405 AC: 101715 AN: 250982 AF XY: 0.409

Gnomad AFR exome AF: 0.508

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.476

Gnomad EAS exome AF: 0.00251

Gnomad FIN exome AF: 0.419

Gnomad NFE exome AF: 0.506

Gnomad OTH exome AF: 0.456

GnomAD4 exome AF: 0.486 AC: 710166 AN: 1461064 Hom.: 183071 Cov.: 58 AF XY: 0.481 AC XY: 349277 AN XY: 726778

African (AFR) AF: 0.511 AC: 17098 AN: 33476

American (AMR) AF: 0.293 AC: 13089 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 12336 AN: 26130

East Asian (EAS) AF: 0.00174 AC: 69 AN: 39626

South Asian (SAS) AF: 0.322 AC: 27685 AN: 85874

European-Finnish (FIN) AF: 0.422 AC: 22482 AN: 53334

Middle Eastern (MID) AF: 0.540 AC: 3113 AN: 5768

European-Non Finnish (NFE) AF: 0.526 AC: 584965 AN: 1111790

Other (OTH) AF: 0.486 AC: 29329 AN: 60344

GnomAD4 genome AF: 0.463 AC: 70295 AN: 151936 Hom.: 17310 Cov.: 31 AF XY: 0.451 AC XY: 33469 AN XY: 74246

African (AFR) AF: 0.509 AC: 21103 AN: 41464

American (AMR) AF: 0.386 AC: 5885 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1635 AN: 3468

East Asian (EAS) AF: 0.00387 AC: 20 AN: 5172

South Asian (SAS) AF: 0.297 AC: 1402 AN: 4726

European-Finnish (FIN) AF: 0.411 AC: 4342 AN: 10562

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34424 AN: 67996

Other (OTH) AF: 0.470 AC: 988 AN: 2102

Alfa AF: 0.490 Hom.: 45070

Bravo AF: 0.464

Asia WGS AF: 0.142 AC: 493 AN: 3416

EpiCase AF: 0.507

EpiControl AF: 0.510

ClinVar

ClinVar submissions

Significance: confers sensitivity

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Familial Otitis Media (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.27
DANN	Benign	0.39
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs485186; hg19: chr19-49207206; COSMIC: COSV67179318; COSMIC: COSV67179318;