2-46612348-GAA-GA

Variant names:

• chr2-46612348-GA-G
• rs747809849
• NM_002643.4:c.321-5delT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002643.4(PIGF):​c.321-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 805,170 control chromosomes in the GnomAD database, including 180 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.027 (143 hom., cov: 32)
  • Exomes 𝑓: 0.020 (37 hom.)
• Consequence: PIGF NM_002643.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210

Genes affected

PIGF (HGNC:8962): (phosphatidylinositol glycan anchor biosynthesis class F) This gene encodes a protein involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor, a glycolipid containing three mannose molecules in its core backbone, is found on many blood cells where it serves to anchor proteins to the cell surface. The encoded protein and another GPI synthesis protein, PIGO, function in the transfer of ethanolaminephosphate to the third mannose in GPI. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGF	NM_002643.4	c.321-5delT		splice_region_variant, intron_variant	Intron 3 of 5	ENST00000281382.11	NP_002634.1
PIGF	NM_173074.3	c.321-5delT		splice_region_variant, intron_variant	Intron 3 of 6		NP_775097.1
PIGF	XM_011532908.4	c.321-5delT		splice_region_variant, intron_variant	Intron 3 of 6		XP_011531210.1
PIGF	XM_005264369.4	c.321-5delT		splice_region_variant, intron_variant	Intron 3 of 5		XP_005264426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGF	ENST00000281382.11	c.321-5delT		splice_region_variant, intron_variant	Intron 3 of 5	1	NM_002643.4	ENSP00000281382.6
PIGF	ENST00000306465.8	c.321-5delT		splice_region_variant, intron_variant	Intron 3 of 6	1		ENSP00000302663.4
PIGF	ENST00000412717.1	n.229-5delT		splice_region_variant, intron_variant	Intron 2 of 4	3		ENSP00000413202.1
PIGF	ENST00000495933.1	n.3338-5delT		splice_region_variant, intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0267 AC: 3555 AN: 133294 Hom.: 143 Cov.: 32

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00814

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000434

Gnomad SAS AF: 0.000708

Gnomad FIN AF: 0.000780

Gnomad MID AF: 0.00365

Gnomad NFE AF: 0.000411

Gnomad OTH AF: 0.0205

GnomAD3 exomes AF: 0.0522 AC: 2906 AN: 55674 Hom.: 17 AF XY: 0.0516 AC XY: 1524 AN XY: 29510

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.0561

Gnomad ASJ exome AF: 0.0570

Gnomad EAS exome AF: 0.0493

Gnomad SAS exome AF: 0.0521

Gnomad FIN exome AF: 0.0122

Gnomad NFE exome AF: 0.0453

Gnomad OTH exome AF: 0.0607

GnomAD4 exome AF: 0.0204 AC: 13713 AN: 671824 Hom.: 37 Cov.: 10 AF XY: 0.0208 AC XY: 7135 AN XY: 342844

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0281

Gnomad4 ASJ exome AF: 0.0206

Gnomad4 EAS exome AF: 0.0183

Gnomad4 SAS exome AF: 0.0313

Gnomad4 FIN exome AF: 0.0133

Gnomad4 NFE exome AF: 0.0172

Gnomad4 OTH exome AF: 0.0252

GnomAD4 genome AF: 0.0267 AC: 3557 AN: 133346 Hom.: 143 Cov.: 32 AF XY: 0.0261 AC XY: 1681 AN XY: 64360

Gnomad4 AFR AF: 0.0928

Gnomad4 AMR AF: 0.00813

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000435

Gnomad4 SAS AF: 0.000711

Gnomad4 FIN AF: 0.000780

Gnomad4 NFE AF: 0.000411

Gnomad4 OTH AF: 0.0204

Bravo AF: 0.0265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs747809849; hg19: chr2-46839487;