rs764959600
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate
The NM_003560.4(PLA2G6):โc.3G>Tโ(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (โ ).
Frequency
Genomes: not found (cov: 32)
Exomes ๐: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PLA2G6
NM_003560.4 start_lost
NM_003560.4 start_lost
Scores
6
7
3
Clinical Significance
Conservation
PhyloP100: 4.96
Genes affected
PLA2G6 (HGNC:9039): (phospholipase A2 group VI) The protein encoded by this gene is an A2 phospholipase, a class of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, fas-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only three of them have been determined to date. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_003560.4 (PLA2G6) was described as [Pathogenic] in ClinVar as 2412655
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 22-38169424-C-A is Pathogenic according to our data. Variant chr22-38169424-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 429031.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLA2G6 | NM_003560.4 | c.3G>T | p.Met1? | start_lost | 2/17 | ENST00000332509.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLA2G6 | ENST00000332509.8 | c.3G>T | p.Met1? | start_lost | 2/17 | 1 | NM_003560.4 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461620Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727116
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1461620
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
727116
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Infantile neuroaxonal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Dr. Faghihi's Medical Genetic Center | Mar 01, 2017 | One and half year-old Afghani boy with muscle weakness at the onset of disease (a case of neuromuscular disease) was addmited to comprehensive children's development in Emam Reza Hospital (Shiraz, Iran) in 2014. He has not been on any treatment until now. Diagnostic evaluations were brain MRI and abdominal and pelvic ultrasonography. There was no intellectual impairment and no hepatosplenomegaly at that age. At the age of two, he showed neurodevelopmental regression (speech, motor and cognition) and floppy infant (hypotonia) but there was no deep tendon reflexes (DTR) and no seizure. The ultrasonography showed normal features but in MRI imaging only a minimal change of periventricular white mater was observed which could be due to mild delayed myelination. Two of his sisters died with similar phenotype at the age of six and four years. Comprehensive laboratory examinations were also requested, including hematology, biochemistry, hormone, and urine analaysis. The positive and abnormal findings for this patient were the decreased level of hemoglobin (Hb) (11.8 g/dL), hematocrit (HCT) (34.5 %), mean corpuscular volume (MCV) (68.73 fL), mean corpuscular hemoglobin (MCH) (23.51 pg), and increased level of CPK (1124 U/L), lactate dehydrogenase (LDH) (542 รยต/L), and aspartate aminotransferase (AST, SGOT) (64 U/L) enzymes. Genetic tests for SMA and DMD diseases showed negative results and therefore whole exom sequencing was suggested to the family. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.;T;T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D;D;.;.;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D
PROVEAN
Benign
N;N;N;N;N;D;D;D;D;.
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D;D;D;D;D;.
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;.;.
Polyphen
D;P;P;.;.;.;.;.;.;.
Vest4
MutPred
Gain of catalytic residue at M1 (P = 0.0387);Gain of catalytic residue at M1 (P = 0.0387);Gain of catalytic residue at M1 (P = 0.0387);Gain of catalytic residue at M1 (P = 0.0387);Gain of catalytic residue at M1 (P = 0.0387);Gain of catalytic residue at M1 (P = 0.0387);Gain of catalytic residue at M1 (P = 0.0387);Gain of catalytic residue at M1 (P = 0.0387);Gain of catalytic residue at M1 (P = 0.0387);Gain of catalytic residue at M1 (P = 0.0387);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at