chr2-46598887-A-C

Variant names:

• chr2-46598887-A-C
• rs17818399
• NM_002643.4:c.438-6304T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002643.4(PIGF):​c.438-6304T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,164 control chromosomes in the GnomAD database, including 6,744 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 0.29 (6744 hom., cov: 32)
• Consequence: PIGF NM_002643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.941
• Publications: 18 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)

LOC124906003 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGF	NM_002643.4	c.438-6304T>G		intron_variant	Intron 4 of 5	ENST00000281382.11	NP_002634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGF	ENST00000281382.11	c.438-6304T>G		intron_variant	Intron 4 of 5	1	NM_002643.4	ENSP00000281382.6
PIGF	ENST00000306465.8	c.438-6304T>G		intron_variant	Intron 4 of 6	1		ENSP00000302663.4
PIGF	ENST00000412717.1	n.*7-6304T>G		intron_variant	Intron 3 of 4	3		ENSP00000413202.1
PIGF	ENST00000420164.6	n.438-6304T>G		intron_variant	Intron 3 of 5	5		ENSP00000410361.2

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44405 AN: 152046 Hom.: 6740 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.293

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44433 AN: 152164 Hom.: 6744 Cov.: 32 AF XY: 0.291 AC XY: 21663 AN XY: 74394

African (AFR) AF: 0.227 AC: 9408 AN: 41520

American (AMR) AF: 0.353 AC: 5390 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1323 AN: 3472

East Asian (EAS) AF: 0.152 AC: 786 AN: 5188

South Asian (SAS) AF: 0.284 AC: 1369 AN: 4824

European-Finnish (FIN) AF: 0.276 AC: 2916 AN: 10568

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22144 AN: 67988

Other (OTH) AF: 0.289 AC: 610 AN: 2114

Alfa AF: 0.264 Hom.: 1992

Bravo AF: 0.290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.44
PhyloP100		0.94
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: rs17818399; hg19: chr2-46826026;