chr2-46614941-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_002643.4(PIGF):c.224A>G(p.His75Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000196 in 1,406,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00088 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

PIGF
NM_002643.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.90

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

PIGF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013887584).

BP6

Variant 2-46614941-T-C is Benign according to our data. Variant chr2-46614941-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3350303.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGF	NM_002643.4 link	c.224A>G	p.His75Arg	missense_variant	Exon 2 of 6	ENST00000281382.11	NP_002634.1	Q07326-1Q6IB04
PIGF	NM_173074.3 link	c.224A>G	p.His75Arg	missense_variant	Exon 2 of 7		NP_775097.1	Q07326-2
PIGF	XM_011532908.4 link	c.224A>G	p.His75Arg	missense_variant	Exon 2 of 7		XP_011531210.1
PIGF	XM_005264369.4 link	c.224A>G	p.His75Arg	missense_variant	Exon 2 of 6		XP_005264426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGF	ENST00000281382.11 link	c.224A>G	p.His75Arg	missense_variant	Exon 2 of 6	1	NM_002643.4	ENSP00000281382.6		Q07326-1

Frequencies

GnomAD3 genomes

AF:

0.000874

AC:

133

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000232

AC:

AN:

250018

AF XY:

0.000170

show subpopulations

Gnomad AFR exome

AF:

0.00285

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000709

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000113

AC:

142

AN:

1254150

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

634102

show subpopulations

African (AFR)

AF:

0.00347

AC:

102

AN:

29376

American (AMR)

AF:

0.000135

AC:

AN:

44380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24826

East Asian (EAS)

AF:

0.0000259

AC:

AN:

38666

South Asian (SAS)

AF:

0.00

AC:

AN:

81922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53280

Middle Eastern (MID)

AF:

0.000186

AC:

AN:

5388

European-Non Finnish (NFE)

AF:

0.0000152

AC:

AN:

922978

Other (OTH)

AF:

0.000337

AC:

AN:

53334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000880

AC:

134

AN:

152356

Hom.:

Cov.:

AF XY:

0.000832

AC XY:

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.00293

AC:

122

AN:

41588

American (AMR)

AF:

0.000523

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000700

Hom.:

Bravo

AF:

0.000948

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000255

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000594

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PIGF-related condition

Benign:1

Apr 02, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.12

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

PhyloP100

3.9

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.13

N;N

REVEL

Benign

0.039

Sift

Benign

0.34

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0020

B;B

Vest4

0.25

MVP

0.25

MPC

0.0059

ClinPred

0.017

GERP RS

3.4

Varity_R

0.12

gMVP

0.55

Mutation Taster

=64/36

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr2-46614941-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over