chr2-46614941-T-C
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_002643.4(PIGF):āc.224A>Gā(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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: š 0.00088 ( 0 hom., cov: 32)
Exomes š: 0.00011 ( 0 hom. )
Consequence
PIGF
NM_002643.4 missense
NM_002643.4 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 3.90
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIGF | NM_002643.4 | c.224A>G | p.His75Arg | missense_variant | 2/6 | ENST00000281382.11 | NP_002634.1 | |
PIGF | NM_173074.3 | c.224A>G | p.His75Arg | missense_variant | 2/7 | NP_775097.1 | ||
PIGF | XM_011532908.4 | c.224A>G | p.His75Arg | missense_variant | 2/7 | XP_011531210.1 | ||
PIGF | XM_005264369.4 | c.224A>G | p.His75Arg | missense_variant | 2/6 | XP_005264426.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIGF | ENST00000281382.11 | c.224A>G | p.His75Arg | missense_variant | 2/6 | 1 | NM_002643.4 | ENSP00000281382 | P1 | |
PIGF | ENST00000306465.8 | c.224A>G | p.His75Arg | missense_variant | 2/7 | 1 | ENSP00000302663 | |||
PIGF | ENST00000495933.1 | n.2090A>G | non_coding_transcript_exon_variant | 1/2 | 2 | |||||
PIGF | ENST00000412717.1 | c.224A>G | p.His75Arg | missense_variant, NMD_transcript_variant | 2/5 | 3 | ENSP00000413202 |
Frequencies
GnomAD3 genomes AF: 0.000874 AC: 133AN: 152238Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000232 AC: 58AN: 250018Hom.: 0 AF XY: 0.000170 AC XY: 23AN XY: 135206
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GnomAD4 exome AF: 0.000113 AC: 142AN: 1254150Hom.: 0 Cov.: 18 AF XY: 0.000110 AC XY: 70AN XY: 634102
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GnomAD4 genome AF: 0.000880 AC: 134AN: 152356Hom.: 0 Cov.: 32 AF XY: 0.000832 AC XY: 62AN XY: 74508
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
PIGF-related condition Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 02, 2024 | 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
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at