chr2-223977558-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001136528.2(SERPINE2):​c.1142G>T​(p.Arg381Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R381Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SERPINE2
NM_001136528.2 missense

Scores

10
8
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.28
Variant links:
Genes affected
SERPINE2 (HGNC:8951): (serpin family E member 2) This gene encodes a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. Thrombin, urokinase, plasmin and trypsin are among the proteases that this family member can inhibit. This gene is a susceptibility gene for chronic obstructive pulmonary disease and for emphysema. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SERPINE2NM_001136528.2 linkc.1142G>T p.Arg381Leu missense_variant Exon 8 of 9 ENST00000409304.6 NP_001130000.1 P07093-2A0A024R498

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SERPINE2ENST00000409304.6 linkc.1142G>T p.Arg381Leu missense_variant Exon 8 of 9 1 NM_001136528.2 ENSP00000386412.1 P07093-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1456498
Hom.:
0
Cov.:
28
AF XY:
0.00000138
AC XY:
1
AN XY:
725012
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Pathogenic
0.43
D
BayesDel_noAF
Pathogenic
0.38
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.82
.;D;.;.
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
.;D;D;D
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.93
D;D;D;D
MetaSVM
Uncertain
0.59
D
MutationAssessor
Uncertain
2.9
.;M;.;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-5.8
D;D;D;D
REVEL
Pathogenic
0.84
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.027
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.91
MutPred
0.77
.;Gain of catalytic residue at F379 (P = 0.2801);.;.;
MVP
0.94
MPC
1.2
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.80
gMVP
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr2-224842275; API