2-223977433-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136528.2(SERPINE2):c.1156+111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 733,070 control chromosomes in the GnomAD database, including 73,863 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 0.37 (12201 hom., cov: 32)
  • Exomes 𝑓: 0.45 (61662 hom.)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE2	NM_001136528.2	c.1156+111A>G		intron_variant		ENST00000409304.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE2	ENST00000409304.6	c.1156+111A>G		intron_variant		1	NM_001136528.2	A1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55877 AN: 151950 Hom.: 12204 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.373

GnomAD4 exome AF: 0.450 AC: 261653 AN: 581002 Hom.: 61662 AF XY: 0.452 AC XY: 141868 AN XY: 313986

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.243

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.549

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.426

GnomAD4 genome AF: 0.367 AC: 55870 AN: 152068 Hom.: 12201 Cov.: 32 AF XY: 0.371 AC XY: 27555 AN XY: 74294

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.368

Alfa AF: 0.430 Hom.: 8518

Bravo AF: 0.340

Asia WGS AF: 0.328 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.045
Dann	Benign	0.47

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: rs7597833; hg19: chr2-224842150; COSMIC: COSV51457691;