2-223980202-C-G

Variant names:

• chr2-223980202-C-G
• rs729631
• NM_001136528.2:c.1072+109G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136528.2(SERPINE2):​c.1072+109G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 886,048 control chromosomes in the GnomAD database, including 273,195 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 0.77 (45299 hom., cov: 33)
  • Exomes 𝑓: 0.78 (227896 hom.)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 11 publications found

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.814 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE2	NM_001136528.2	MANE Select	c.1072+109G>C		intron	N/A	NP_001130000.1	P07093-2
	SERPINE2	NM_001136530.1		c.1108+109G>C		intron	N/A	NP_001130002.1	P07093-3
	SERPINE2	NM_006216.4		c.1075+109G>C		intron	N/A	NP_006207.1	P07093-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE2	ENST00000409304.6	TSL:1 MANE Select	c.1072+109G>C		intron	N/A	ENSP00000386412.1	P07093-2
	SERPINE2	ENST00000258405.9	TSL:1	c.1075+109G>C		intron	N/A	ENSP00000258405.4	P07093-1
	SERPINE2	ENST00000409840.7	TSL:1	c.1072+109G>C		intron	N/A	ENSP00000386969.3	P07093-2

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116644 AN: 152056 Hom.: 45274 Cov.: 33

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.766

GnomAD4 exome AF: 0.782 AC: 574194 AN: 733874 Hom.: 227896 Cov.: 10 AF XY: 0.777 AC XY: 299220 AN XY: 385142

African (AFR) AF: 0.709 AC: 13439 AN: 18950

American (AMR) AF: 0.838 AC: 31660 AN: 37770

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 13590 AN: 19130

East Asian (EAS) AF: 0.450 AC: 15167 AN: 33670

South Asian (SAS) AF: 0.684 AC: 43579 AN: 63742

European-Finnish (FIN) AF: 0.794 AC: 38921 AN: 49048

Middle Eastern (MID) AF: 0.698 AC: 2305 AN: 3302

European-Non Finnish (NFE) AF: 0.822 AC: 388216 AN: 472538

Other (OTH) AF: 0.765 AC: 27317 AN: 35724

GnomAD4 genome AF: 0.767 AC: 116723 AN: 152174 Hom.: 45299 Cov.: 33 AF XY: 0.763 AC XY: 56749 AN XY: 74402

African (AFR) AF: 0.713 AC: 29604 AN: 41498

American (AMR) AF: 0.808 AC: 12357 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2479 AN: 3470

East Asian (EAS) AF: 0.445 AC: 2300 AN: 5172

South Asian (SAS) AF: 0.671 AC: 3237 AN: 4822

European-Finnish (FIN) AF: 0.790 AC: 8362 AN: 10586

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.820 AC: 55763 AN: 68014

Other (OTH) AF: 0.757 AC: 1599 AN: 2112

Alfa AF: 0.762 Hom.: 2360

Bravo AF: 0.768

Asia WGS AF: 0.552 AC: 1922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.41
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs729631; hg19: chr2-224844919; COSMIC: COSV51457664; COSMIC: COSV51457664;