rs34078713

Variant names:

• chr2-224001710-A-G
• rs34078713
• NM_001136528.2:c.191T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BP4_Strong BS2

The NM_001136528.2(SERPINE2):​c.191T>C​(p.Met64Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00834 in 1,614,172 control chromosomes in the GnomAD database, including 70 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 0.0075 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (60 hom.)
• Consequence: SERPINE2 NM_001136528.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.37

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]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.017178237).
• BS2: High AC in GnomAd4 at 1144 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.191T>C	p.Met64Thr	missense_variant	Exon 2 of 9	ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.191T>C	p.Met64Thr	missense_variant	Exon 2 of 9	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.00752 AC: 1144 AN: 152186 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00750 AC: 1883 AN: 251216 AF XY: 0.00780

Gnomad AFR exome AF: 0.00160

Gnomad AMR exome AF: 0.00717

Gnomad ASJ exome AF: 0.00824

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0103

Gnomad NFE exome AF: 0.0108

Gnomad OTH exome AF: 0.00849

GnomAD4 exome AF: 0.00843 AC: 12318 AN: 1461868 Hom.: 60 Cov.: 33 AF XY: 0.00829 AC XY: 6032 AN XY: 727240

Gnomad4 AFR exome AF: 0.00102 AC: 34 AN: 33480

Gnomad4 AMR exome AF: 0.00709 AC: 317 AN: 44724

Gnomad4 ASJ exome AF: 0.00761 AC: 199 AN: 26136

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.000707 AC: 61 AN: 86258

Gnomad4 FIN exome AF: 0.0111 AC: 594 AN: 53398

Gnomad4 NFE exome AF: 0.00958 AC: 10657 AN: 1112008

Gnomad4 Remaining exome AF: 0.00720 AC: 435 AN: 60396

GnomAD4 genome AF: 0.00751 AC: 1144 AN: 152304 Hom.: 10 Cov.: 32 AF XY: 0.00760 AC XY: 566 AN XY: 74468

Gnomad4 AFR AF: 0.00168 AC: 0.00168366 AN: 0.00168366

Gnomad4 AMR AF: 0.0113 AC: 0.0113013 AN: 0.0113013

Gnomad4 ASJ AF: 0.00806 AC: 0.00806452 AN: 0.00806452

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00104 AC: 0.00103648 AN: 0.00103648

Gnomad4 FIN AF: 0.0108 AC: 0.0108347 AN: 0.0108347

Gnomad4 NFE AF: 0.0102 AC: 0.0101726 AN: 0.0101726

Gnomad4 OTH AF: 0.00615 AC: 0.00614948 AN: 0.00614948

Alfa AF: 0.00875 Hom.: 15

Bravo AF: 0.00721

TwinsUK AF: 0.00944 AC: 35

ALSPAC AF: 0.00934 AC: 36

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.0109 AC: 94

ExAC AF: 0.00751 AC: 912

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00829

EpiControl AF: 0.0122

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.86	.;D;.;.;T;T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.88	.;D;D;D;D;D
MetaRNN	Benign	0.017	T;T;T;T;T;T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Pathogenic	3.5	H;H;H;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.6	D;D;D;D;D;D
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0020	D;D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;.;.
Polyphen		0.93	.;P;.;.;.;.
Vest4		0.55
MVP		0.68
MPC		0.89
ClinPred		0.038	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.85
gMVP		0.94
Mutation Taster		=99/1	polymorphism

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

LitVar

Other links and lift over

dbSNP: rs34078713; hg19: chr2-224866427;