chr11-57389272-A-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002728.6(PRG2):c.104T>A(p.Leu35Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000038 ( 0 hom. )
Consequence
PRG2
NM_002728.6 missense
NM_002728.6 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 0.646
Genes affected
PRG2 (HGNC:9362): (proteoglycan 2, pro eosinophil major basic protein) The protein encoded by this gene is the predominant constituent of the crystalline core of the eosinophil granule. High levels of the proform of this protein are also present in placenta and pregnancy serum, where it exists as a complex with several other proteins including pregnancy-associated plasma protein A (PAPPA), angiotensinogen (AGT), and C3dg. This protein may be involved in antiparasitic defense mechanisms as a cytotoxin and helminthotoxin, and in immune hypersensitivity reactions. The encoded protein contains a peptide that displays potent antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, and fungi. It is directly implicated in epithelial cell damage, exfoliation, and bronchospasm in allergic diseases. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.027194679).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRG2 | NM_002728.6 | c.104T>A | p.Leu35Gln | missense_variant | 3/6 | ENST00000311862.10 | |
PRG2 | NM_001302926.2 | c.104T>A | p.Leu35Gln | missense_variant | 3/6 | ||
PRG2 | NM_001302927.2 | c.104T>A | p.Leu35Gln | missense_variant | 3/6 | ||
PRG2 | NM_001243245.3 | c.104T>A | p.Leu35Gln | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRG2 | ENST00000311862.10 | c.104T>A | p.Leu35Gln | missense_variant | 3/6 | 1 | NM_002728.6 | P1 | |
PRG2 | ENST00000525955.1 | c.104T>A | p.Leu35Gln | missense_variant | 3/6 | 2 | P1 | ||
PRG2 | ENST00000533605.5 | c.104T>A | p.Leu35Gln | missense_variant | 3/6 | 5 | |||
PRG2 | ENST00000530105.1 | n.150T>A | non_coding_transcript_exon_variant | 3/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152146Hom.: 0 Cov.: 32
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?
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GnomAD3 exomes AF: 0.0000995 AC: 25AN: 251176Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135752
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GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461672Hom.: 0 Cov.: 33 AF XY: 0.0000481 AC XY: 35AN XY: 727142
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74308
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 21, 2021 | The c.104T>A (p.L35Q) alteration is located in exon 3 (coding exon 2) of the PRG2 gene. This alteration results from a T to A substitution at nucleotide position 104, causing the leucine (L) at amino acid position 35 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
D;.;D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.
MutationTaster
Benign
N;N;N
PROVEAN
Uncertain
D;D;D;N
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Benign
T;T;T;D
Polyphen
D;.;D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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