2-46612348-GAA-GAAAA

Variant names:

• chr2-46612348-G-GAA
• rs747809849
• NM_002643.4:c.321-6_321-5dupTT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_002643.4(PIGF):​c.321-6_321-5dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (0 hom.)
  • Failed GnomAD Quality Control
• 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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGF	NM_002643.4	c.321-6_321-5dupTT		splice_region_variant, intron_variant	Intron 3 of 5	ENST00000281382.11	NP_002634.1
PIGF	NM_173074.3	c.321-6_321-5dupTT		splice_region_variant, intron_variant	Intron 3 of 6		NP_775097.1
PIGF	XM_011532908.4	c.321-6_321-5dupTT		splice_region_variant, intron_variant	Intron 3 of 6		XP_011531210.1
PIGF	XM_005264369.4	c.321-6_321-5dupTT		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.321-5_321-4insTT		splice_region_variant, intron_variant	Intron 3 of 5	1	NM_002643.4	ENSP00000281382.6
PIGF	ENST00000306465.8	c.321-5_321-4insTT		splice_region_variant, intron_variant	Intron 3 of 6	1		ENSP00000302663.4
PIGF	ENST00000412717.1	n.229-5_229-4insTT		splice_region_variant, intron_variant	Intron 2 of 4	3		ENSP00000413202.1
PIGF	ENST00000495933.1	n.3338-5_3338-4insTT		splice_region_variant, intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 133364 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000575 AC: 32 AN: 55674 Hom.: 0 AF XY: 0.000576 AC XY: 17 AN XY: 29510

Gnomad AFR exome AF: 0.000686

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.000532

Gnomad EAS exome AF: 0.00109

Gnomad SAS exome AF: 0.000541

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000484

Gnomad OTH exome AF: 0.000906

GnomAD4 exome AF: 0.000321 AC: 224 AN: 698532 Hom.: 0 Cov.: 10 AF XY: 0.000350 AC XY: 125 AN XY: 357280

Gnomad4 AFR exome AF: 0.000193

Gnomad4 AMR exome AF: 0.000443

Gnomad4 ASJ exome AF: 0.000293

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.000718

Gnomad4 FIN exome AF: 0.000219

Gnomad4 NFE exome AF: 0.000303

Gnomad4 OTH exome AF: 0.000400

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 133364 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 64334

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;