chr2-46612348-G-GAA

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

PIGF Gene-Disease associations (from GenCC):

• onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 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

Frequencies

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

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

GnomAD2 exomes AF: 0.000575 AC: 32 AN: 55674 AF XY: 0.000576

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000193 AC: 3 AN: 15534

American (AMR) AF: 0.000443 AC: 7 AN: 15792

Ashkenazi Jewish (ASJ) AF: 0.000293 AC: 4 AN: 13640

East Asian (EAS) AF: 0.000129 AC: 3 AN: 23184

South Asian (SAS) AF: 0.000718 AC: 30 AN: 41804

European-Finnish (FIN) AF: 0.000219 AC: 8 AN: 36574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3638

European-Non Finnish (NFE) AF: 0.000303 AC: 157 AN: 518368

Other (OTH) AF: 0.000400 AC: 12 AN: 29998

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.00 AC: 0 AN: 36282

American (AMR) AF: 0.00 AC: 0 AN: 13526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3172

East Asian (EAS) AF: 0.00 AC: 0 AN: 4612

South Asian (SAS) AF: 0.00 AC: 0 AN: 4238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60890

Other (OTH) AF: 0.00 AC: 0 AN: 1810

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs747809849; hg19: chr2-46839487;