rs2838859

Positions:

• chr21-45264602-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133635.6(POFUT2):​c.*880G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,918 control chromosomes in the GnomAD database, including 13,492 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (13478 hom., cov: 31)
  • Exomes 𝑓: 0.34 (14 hom.)
• Consequence: POFUT2 NM_133635.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

Genes affected

POFUT2 (HGNC:14683): (protein O-fucosyltransferase 2) Fucose is typically found as a terminal modification of branched chain glycoconjugates, but it also exists in direct O-linkage to serine or threonine residues within cystine knot motifs in epidermal growth factor (EGF; MIM 131530)-like repeats or thrombospondin (THBS; see MIM 188060) type-1 repeats. POFUT2 is an O-fucosyltransferase that use THBS type-1 repeats as substrates (Luo et al., 2006 [PubMed 16464857]).[supplied by OMIM, Mar 2008]

POFUT2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POFUT2	NM_133635.6	c.*880G>A		3_prime_UTR_variant	9/9	ENST00000349485.10	NP_598368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POFUT2	ENST00000349485	c.*880G>A		3_prime_UTR_variant	9/9	1	NM_133635.6	ENSP00000339613.5

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62627 AN: 151526 Hom.: 13459 Cov.: 31

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.343 AC: 94 AN: 274 Hom.: 14 Cov.: 0 AF XY: 0.332 AC XY: 69 AN XY: 208

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.413 AC: 62695 AN: 151644 Hom.: 13478 Cov.: 31 AF XY: 0.417 AC XY: 30876 AN XY: 74104

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.409

Alfa AF: 0.376 Hom.: 17849

Bravo AF: 0.414

Asia WGS AF: 0.487 AC: 1696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2838859; hg19: chr21-46684517;