Genetic Variant SERPINE2:c.985+1005G>A (chr2-223981676-C-T) – 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+1005G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,076 control chromosomes in the GnomAD database, including 6,650 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 ( 6650 hom., cov: 33)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

SERPINE2
NM_001136528.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.771

Publications

2 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:

Genome browser will be placed here

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=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.392 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	UniProt
SERPINE2	NM_001136528.2	MANE Select	c.985+1005G>A	intron	N/A	NP_001130000.1	P07093-2
SERPINE2	NM_001136530.1		c.1021+1005G>A	intron	N/A	NP_001130002.1	P07093-3
SERPINE2	NM_006216.4		c.985+1005G>A	intron	N/A	NP_006207.1	P07093-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SERPINE2	ENST00000409304.6	TSL:1 MANE Select	c.985+1005G>A	intron	N/A	ENSP00000386412.1	P07093-2
SERPINE2	ENST00000258405.9	TSL:1	c.985+1005G>A	intron	N/A	ENSP00000258405.4	P07093-1
SERPINE2	ENST00000409840.7	TSL:1	c.985+1005G>A	intron	N/A	ENSP00000386969.3	P07093-2

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40259

AN:

151950

Hom.:

6654

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0651

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.407

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.223

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.258

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.265

AC:

40254

AN:

152068

Hom.:

6650

Cov.:

AF XY:

0.269

AC XY:

20017

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.0650

AC:

2698

AN:

41522

American (AMR)

AF:

0.300

AC:

4583

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

649

AN:

3470

East Asian (EAS)

AF:

0.221

AC:

1145

AN:

5172

South Asian (SAS)

AF:

0.407

AC:

1961

AN:

4818

European-Finnish (FIN)

AF:

0.433

AC:

4562

AN:

10540

Middle Eastern (MID)

AF:

0.219

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.350

AC:

23800

AN:

67946

Other (OTH)

AF:

0.254

AC:

535

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1421

2842

4263

5684

7105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

418

836

1254

1672

2090

<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:

0.244

Hom.:

3149

Bravo

AF:

0.242

Asia WGS

AF:

0.279

AC:

971

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.1

(source)

DANN

Benign

0.52

PhyloP100

-0.77

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over