rs764274557

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020318.3(PAPPA2):​c.280C>A​(p.Arg94Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R94C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PAPPA2
NM_020318.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.324
Variant links:
Genes affected
PAPPA2 (HGNC:14615): (pappalysin 2) This gene encodes a member of the pappalysin family of metzincin metalloproteinases. The encoded protein cleaves insulin-like growth factor-binding protein 5 and is thought to be a local regulator of insulin-like growth factor (IGF) bioavailability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

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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=0.05537331).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PAPPA2NM_020318.3 linkc.280C>A p.Arg94Ser missense_variant Exon 2 of 23 ENST00000367662.5 NP_064714.2 Q9BXP8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PAPPA2ENST00000367662.5 linkc.280C>A p.Arg94Ser missense_variant Exon 2 of 23 1 NM_020318.3 ENSP00000356634.3 Q9BXP8-1
PAPPA2ENST00000367661.7 linkc.280C>A p.Arg94Ser missense_variant Exon 2 of 5 1 ENSP00000356633.3 Q9BXP8-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
1.2
DANN
Benign
0.64
DEOGEN2
Benign
0.056
.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.46
T;T
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.055
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N;N
PrimateAI
Benign
0.18
T
PROVEAN
Benign
-0.35
N;N
REVEL
Benign
0.038
Sift
Benign
0.59
T;T
Sift4G
Benign
0.48
T;T
Polyphen
0.013
.;B
Vest4
0.10
MutPred
0.18
Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP
0.24
MPC
0.20
ClinPred
0.030
T
GERP RS
-1.0
Varity_R
0.085
gMVP
0.22

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.

Other links and lift over

hg19: chr1-176525738; API