2-224013584-A-G

Variant names:

• chr2-224013584-A-G
• rs1438828
• NM_001136528.2:c.-22-11662T>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.-22-11662T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,108 control chromosomes in the GnomAD database, including 1,286 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 0.12 (1286 hom., cov: 32)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 7 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]

ENSG00000310283 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 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.-22-11662T>C		intron	N/A	NP_001130000.1	P07093-2
	SERPINE2	NM_001136530.1		c.15-11662T>C		intron	N/A	NP_001130002.1	P07093-3
	SERPINE2	NM_006216.4		c.-22-11662T>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.-22-11662T>C		intron	N/A	ENSP00000386412.1	P07093-2
	SERPINE2	ENST00000258405.9	TSL:1	c.-22-11662T>C		intron	N/A	ENSP00000258405.4	P07093-1
	SERPINE2	ENST00000409840.7	TSL:1	c.-22-11662T>C		intron	N/A	ENSP00000386969.3	P07093-2

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18686 AN: 151990 Hom.: 1280 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0860

Gnomad OTH AF: 0.105

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18731 AN: 152108 Hom.: 1286 Cov.: 32 AF XY: 0.126 AC XY: 9398 AN XY: 74382

African (AFR) AF: 0.163 AC: 6745 AN: 41462

American (AMR) AF: 0.142 AC: 2175 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3468

East Asian (EAS) AF: 0.205 AC: 1059 AN: 5172

South Asian (SAS) AF: 0.151 AC: 725 AN: 4816

European-Finnish (FIN) AF: 0.123 AC: 1305 AN: 10596

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0860 AC: 5849 AN: 67998

Other (OTH) AF: 0.105 AC: 221 AN: 2110

Alfa AF: 0.100 Hom.: 1080

Bravo AF: 0.125

Asia WGS AF: 0.155 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.82
PhyloP100		0.077
PromoterAI		0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1438828; hg19: chr2-224878301;