chr2-224001859-C-A

Position:

• chr2-224001859-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001136528.2(SERPINE2):​c.42G>T​(p.Thr14=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,650 control chromosomes in the GnomAD database, including 16,197 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 0.18 (3093 hom., cov: 32)
  • Exomes 𝑓: 0.12 (13104 hom.)
• Consequence: SERPINE2 NM_001136528.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.651 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE2	NM_001136528.2	c.42G>T	p.Thr14=	synonymous_variant	2/9	ENST00000409304.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE2	ENST00000409304.6	c.42G>T	p.Thr14=	synonymous_variant	2/9	1	NM_001136528.2	A1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27575 AN: 151906 Hom.: 3081 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.156

GnomAD3 exomes AF: 0.160 AC: 40240 AN: 251394 Hom.: 3760 AF XY: 0.156 AC XY: 21238 AN XY: 135876

Gnomad AFR exome AF: 0.309

Gnomad AMR exome AF: 0.205

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.229

Gnomad SAS exome AF: 0.210

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.124 AC: 181124 AN: 1461626 Hom.: 13104 Cov.: 33 AF XY: 0.126 AC XY: 91709 AN XY: 727102

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.128

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.182 AC: 27635 AN: 152024 Hom.: 3093 Cov.: 32 AF XY: 0.184 AC XY: 13645 AN XY: 74310

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.155

Alfa AF: 0.130 Hom.: 2072

Bravo AF: 0.190

Asia WGS AF: 0.204 AC: 710 AN: 3478

EpiCase AF: 0.105

EpiControl AF: 0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.40
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12436; hg19: chr2-224866576; COSMIC: COSV51456418;