Genetic Variant SERPINE2:c.985+130A>G (chr2-223982551-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001136528.2(SERPINE2):c.985+130A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 490,612 control chromosomes in the GnomAD database, including 15,980 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 0.22 ( 4197 hom., cov: 33)

Exomes 𝑓: 0.25 ( 11783 hom. )

Consequence

SERPINE2
NM_001136528.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0890

Publications

6 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]

SERPINE2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136528.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SERPINE2	NM_001136528.2	MANE Select	c.985+130A>G	intron	N/A	NP_001130000.1
SERPINE2	NM_001136530.1		c.1021+130A>G	intron	N/A	NP_001130002.1
SERPINE2	NM_006216.4		c.985+130A>G	intron	N/A	NP_006207.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SERPINE2	ENST00000409304.6	TSL:1 MANE Select	c.985+130A>G	intron	N/A	ENSP00000386412.1
SERPINE2	ENST00000258405.9	TSL:1	c.985+130A>G	intron	N/A	ENSP00000258405.4
SERPINE2	ENST00000409840.7	TSL:1	c.985+130A>G	intron	N/A	ENSP00000386969.3

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32869

AN:

152082

Hom.:

4201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.479

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.0175

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.229

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.224

GnomAD4 exome

AF:

0.248

AC:

83920

AN:

338412

Hom.:

11783

Cov.:

AF XY:

0.246

AC XY:

43484

AN XY:

176866

show subpopulations

African (AFR)

AF:

0.0946

AC:

807

AN:

8528

American (AMR)

AF:

0.162

AC:

1653

AN:

10174

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

2794

AN:

10804

East Asian (EAS)

AF:

0.0470

AC:

1167

AN:

24820

South Asian (SAS)

AF:

0.139

AC:

3066

AN:

22096

European-Finnish (FIN)

AF:

0.231

AC:

6822

AN:

29492

Middle Eastern (MID)

AF:

0.223

AC:

347

AN:

1554

European-Non Finnish (NFE)

AF:

0.296

AC:

62457

AN:

210678

Other (OTH)

AF:

0.237

AC:

4807

AN:

20266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2817

5633

8450

11266

14083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.216

AC:

32863

AN:

152200

Hom.:

4197

Cov.:

AF XY:

0.209

AC XY:

15582

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.107

AC:

4425

AN:

41534

American (AMR)

AF:

0.186

AC:

2844

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

951

AN:

3466

East Asian (EAS)

AF:

0.0175

AC:

AN:

5188

South Asian (SAS)

AF:

0.141

AC:

680

AN:

4824

European-Finnish (FIN)

AF:

0.223

AC:

2363

AN:

10584

Middle Eastern (MID)

AF:

0.216

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.302

AC:

20538

AN:

67982

Other (OTH)

AF:

0.223

AC:

471

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1278

2557

3835

5114

6392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.263

Hom.:

10039

Bravo

AF:

0.211

Asia WGS

AF:

0.0920

AC:

323

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.19

(source)

DANN

Benign

0.39

PhyloP100

-0.089

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over