Genetic Variant NM_001136528.2:c.871G>C (chr2-223984765-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001136528.2(SERPINE2):c.871G>C(p.Val291Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SERPINE2
NM_001136528.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.39

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09394616).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINE2	NM_001136528.2	MANE Select	c.871G>C	p.Val291Leu	missense	Exon 5 of 9	NP_001130000.1	P07093-2
SERPINE2	NM_001136530.1		c.907G>C	p.Val303Leu	missense	Exon 5 of 9	NP_001130002.1	P07093-3
SERPINE2	NM_006216.4		c.871G>C	p.Val291Leu	missense	Exon 5 of 9	NP_006207.1	P07093-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINE2	ENST00000409304.6	TSL:1 MANE Select	c.871G>C	p.Val291Leu	missense	Exon 5 of 9	ENSP00000386412.1	P07093-2
SERPINE2	ENST00000258405.9	TSL:1	c.871G>C	p.Val291Leu	missense	Exon 5 of 9	ENSP00000258405.4	P07093-1
SERPINE2	ENST00000409840.7	TSL:1	c.871G>C	p.Val291Leu	missense	Exon 6 of 10	ENSP00000386969.3	P07093-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460256

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111786

Other (OTH)

AF:

0.00

AC:

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.38

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.83

M_CAP

Benign

0.014

MetaRNN

Benign

0.094

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.43

PhyloP100

2.4

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.030

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0030

Vest4

0.15

MutPred

0.57

Loss of methylation at K287 (P = 0.0776)

MVP

0.33

MPC

0.32

ClinPred

0.24

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.074

gMVP

0.60

Mutation Taster

=84/16

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over