2-46593663-G-C

Variant names:

• chr2-46593663-G-C
• rs3768725
• NM_002643.4:c.438-1080C>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.438-1080C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 151,994 control chromosomes in the GnomAD database, including 4,143 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 0.18 (4143 hom., cov: 32)
• Consequence: PIGF NM_002643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 3 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), ClinGen

LOC124906003 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002643.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGF	NM_002643.4	MANE Select	c.438-1080C>G		intron	N/A	NP_002634.1	Q6IB04
	PIGF	NM_173074.3		c.438-1080C>G		intron	N/A	NP_775097.1	Q07326-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGF	ENST00000281382.11	TSL:1 MANE Select	c.438-1080C>G		intron	N/A	ENSP00000281382.6	Q07326-1
	PIGF	ENST00000306465.8	TSL:1	c.438-1080C>G		intron	N/A	ENSP00000302663.4	Q07326-2
	PIGF	ENST00000903157.1		c.438-1080C>G		intron	N/A	ENSP00000573216.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27181 AN: 151876 Hom.: 4130 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.179 AC: 27231 AN: 151994 Hom.: 4143 Cov.: 32 AF XY: 0.173 AC XY: 12895 AN XY: 74344

African (AFR) AF: 0.419 AC: 17296 AN: 41276

American (AMR) AF: 0.118 AC: 1811 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3468

East Asian (EAS) AF: 0.0399 AC: 207 AN: 5182

South Asian (SAS) AF: 0.151 AC: 730 AN: 4830

European-Finnish (FIN) AF: 0.0461 AC: 489 AN: 10614

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0874 AC: 5945 AN: 68008

Other (OTH) AF: 0.147 AC: 312 AN: 2116

Alfa AF: 0.0483 Hom.: 59

Bravo AF: 0.196

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.55
PhyloP100		-0.040
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: rs3768725; hg19: chr2-46820802;