Variant chr2-46592506-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PS1_ModeratePM2PP3_StrongPP5

The NM_002643.4(PIGF):c.515C>G(p.Pro172Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PIGF
NM_002643.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.96

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PS1

Transcript NM_002643.4 (PIGF) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.981

PP5

Variant 2-46592506-G-C is Pathogenic according to our data. Variant chr2-46592506-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 1162290.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PIGF	NM_002643.4 linkuse as main transcript	c.515C>G	p.Pro172Arg	missense_variant	5/6	ENST00000281382.11	NP_002634.1
PIGF	NM_173074.3 linkuse as main transcript	c.515C>G	p.Pro172Arg	missense_variant	5/7		NP_775097.1
PIGF	XM_011532908.4 linkuse as main transcript	c.515C>G	p.Pro172Arg	missense_variant	5/7		XP_011531210.1
PIGF	XM_005264369.4 linkuse as main transcript	c.515C>G	p.Pro172Arg	missense_variant	5/6		XP_005264426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGF	ENST00000281382.11 linkuse as main transcript	c.515C>G	p.Pro172Arg	missense_variant	5/6	1	NM_002643.4	ENSP00000281382	P1	Q07326-1
PIGF	ENST00000306465.8 linkuse as main transcript	c.515C>G	p.Pro172Arg	missense_variant	5/7	1		ENSP00000302663		Q07326-2
PIGF	ENST00000420164.5 linkuse as main transcript	c.125C>G	p.Pro42Arg	missense_variant, NMD_transcript_variant	2/4	5		ENSP00000410361
PIGF	ENST00000412717.1 linkuse as main transcript	c.*84C>G		3_prime_UTR_variant, NMD_transcript_variant	4/5	3		ENSP00000413202

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723834

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Pathogenic

0.49

BayesDel_noAF

Pathogenic

0.46

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;.

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.98

D;D

MetaSVM

Uncertain

0.31

MutationAssessor

Pathogenic

3.6

H;H

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-7.0

D;D

REVEL

Pathogenic

0.85

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;D

Vest4

0.98

MutPred

0.88

Gain of MoRF binding (P = 0.0815);Gain of MoRF binding (P = 0.0815);

MVP

0.73

MPC

0.032

ClinPred

1.0

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.96

gMVP

0.96

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over