chr2-223998125-A-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001136528.2(SERPINE2):​c.477T>C​(p.Asn159Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,612,994 control chromosomes in the GnomAD database, including 38,675 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 6405 hom., cov: 33)
Exomes 𝑓: 0.20 ( 32270 hom. )

Consequence

SERPINE2
NM_001136528.2 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.338

Publications

14 publications found
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP7
Synonymous conserved (PhyloP=0.338 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SERPINE2NM_001136528.2 linkc.477T>C p.Asn159Asn synonymous_variant Exon 3 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.477T>C p.Asn159Asn synonymous_variant Exon 3 of 9 1 NM_001136528.2 ENSP00000386412.1 P07093-2

Frequencies

GnomAD3 genomes
AF:
0.263
AC:
39996
AN:
152038
Hom.:
6391
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.454
Gnomad AMI
AF:
0.222
Gnomad AMR
AF:
0.216
Gnomad ASJ
AF:
0.243
Gnomad EAS
AF:
0.140
Gnomad SAS
AF:
0.167
Gnomad FIN
AF:
0.111
Gnomad MID
AF:
0.285
Gnomad NFE
AF:
0.199
Gnomad OTH
AF:
0.267
GnomAD2 exomes
AF:
0.197
AC:
49459
AN:
251120
AF XY:
0.196
show subpopulations
Gnomad AFR exome
AF:
0.456
Gnomad AMR exome
AF:
0.146
Gnomad ASJ exome
AF:
0.240
Gnomad EAS exome
AF:
0.135
Gnomad FIN exome
AF:
0.112
Gnomad NFE exome
AF:
0.205
Gnomad OTH exome
AF:
0.205
GnomAD4 exome
AF:
0.203
AC:
295851
AN:
1460838
Hom.:
32270
Cov.:
32
AF XY:
0.202
AC XY:
146815
AN XY:
726750
show subpopulations
African (AFR)
AF:
0.464
AC:
15538
AN:
33454
American (AMR)
AF:
0.154
AC:
6894
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.243
AC:
6340
AN:
26132
East Asian (EAS)
AF:
0.156
AC:
6209
AN:
39694
South Asian (SAS)
AF:
0.176
AC:
15153
AN:
86240
European-Finnish (FIN)
AF:
0.114
AC:
6109
AN:
53410
Middle Eastern (MID)
AF:
0.294
AC:
1694
AN:
5766
European-Non Finnish (NFE)
AF:
0.202
AC:
224804
AN:
1111058
Other (OTH)
AF:
0.217
AC:
13110
AN:
60368
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.478
Heterozygous variant carriers
0
11816
23632
35448
47264
59080
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
7878
15756
23634
31512
39390
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.263
AC:
40043
AN:
152156
Hom.:
6405
Cov.:
33
AF XY:
0.258
AC XY:
19187
AN XY:
74394
show subpopulations
African (AFR)
AF:
0.455
AC:
18853
AN:
41478
American (AMR)
AF:
0.215
AC:
3293
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
0.243
AC:
844
AN:
3472
East Asian (EAS)
AF:
0.140
AC:
726
AN:
5176
South Asian (SAS)
AF:
0.166
AC:
800
AN:
4826
European-Finnish (FIN)
AF:
0.111
AC:
1174
AN:
10600
Middle Eastern (MID)
AF:
0.259
AC:
76
AN:
294
European-Non Finnish (NFE)
AF:
0.199
AC:
13517
AN:
67986
Other (OTH)
AF:
0.264
AC:
558
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1447
2894
4341
5788
7235
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
396
792
1188
1584
1980
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.225
Hom.:
15383
Bravo
AF:
0.282
Asia WGS
AF:
0.138
AC:
479
AN:
3478
EpiCase
AF:
0.213
EpiControl
AF:
0.221

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
2.4
DANN
Benign
0.53
PhyloP100
0.34
Mutation Taster
=92/8
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12457; hg19: chr2-224862842; COSMIC: COSV51456455; COSMIC: COSV51456455; API