2-46590505-T-C

Variant names:

• chr2-46590505-T-C
• rs896213
• NM_002643.4:c.546+1970A>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.546+1970A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 149,952 control chromosomes in the GnomAD database, including 39,061 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 0.72 (39061 hom., cov: 32)
• Consequence: PIGF NM_002643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGF	NM_002643.4	c.546+1970A>G		intron_variant	Intron 5 of 5	ENST00000281382.11	NP_002634.1
PIGF	NM_173074.3	c.546+1970A>G		intron_variant	Intron 5 of 6		NP_775097.1
PIGF	XM_011532908.4	c.546+1970A>G		intron_variant	Intron 5 of 6		XP_011531210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGF	ENST00000281382.11	c.546+1970A>G		intron_variant	Intron 5 of 5	1	NM_002643.4	ENSP00000281382.6
PIGF	ENST00000306465.8	c.546+1970A>G		intron_variant	Intron 5 of 6	1		ENSP00000302663.4
PIGF	ENST00000412717.1	n.*115+1970A>G		intron_variant	Intron 4 of 4	3		ENSP00000413202.1
PIGF	ENST00000420164.6	n.*105+1298A>G		intron_variant	Intron 5 of 5	5		ENSP00000410361.2

Frequencies

GnomAD3 genomes AF: 0.718 AC: 107624 AN: 149834 Hom.: 39002 Cov.: 32

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.718 AC: 107737 AN: 149952 Hom.: 39061 Cov.: 32 AF XY: 0.718 AC XY: 52524 AN XY: 73112

African (AFR) AF: 0.872 AC: 36086 AN: 41380

American (AMR) AF: 0.736 AC: 10998 AN: 14950

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2246 AN: 3432

East Asian (EAS) AF: 0.700 AC: 3567 AN: 5098

South Asian (SAS) AF: 0.670 AC: 3116 AN: 4652

European-Finnish (FIN) AF: 0.641 AC: 6537 AN: 10194

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.642 AC: 43016 AN: 67010

Other (OTH) AF: 0.706 AC: 1446 AN: 2048

Alfa AF: 0.700 Hom.: 7698

Bravo AF: 0.726

Asia WGS AF: 0.694 AC: 2408 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.48
PhyloP100		-0.71
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: rs896213; hg19: chr2-46817644;