2-224018588-C-T

Variant names:

• chr2-224018588-C-T
• rs2037755
• NM_001136528.2:c.-22-16666G>A

Variant summary

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

The NM_001136528.2(SERPINE2):​c.-22-16666G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 147,122 control chromosomes in the GnomAD database, including 16,216 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 0.44 (16216 hom., cov: 27)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.563 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.-22-16666G>A		intron	N/A	NP_001130000.1	P07093-2
	SERPINE2	NM_001136530.1		c.15-16666G>A		intron	N/A	NP_001130002.1	P07093-3
	SERPINE2	NM_006216.4		c.-22-16666G>A		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.-22-16666G>A		intron	N/A	ENSP00000386412.1	P07093-2
	SERPINE2	ENST00000258405.9	TSL:1	c.-22-16666G>A		intron	N/A	ENSP00000258405.4	P07093-1
	SERPINE2	ENST00000409840.7	TSL:1	c.-23+11484G>A		intron	N/A	ENSP00000386969.3	P07093-2

Frequencies

GnomAD3 genomes AF: 0.438 AC: 64430 AN: 147010 Hom.: 16228 Cov.: 27

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.438 AC: 64427 AN: 147122 Hom.: 16216 Cov.: 27 AF XY: 0.445 AC XY: 31925 AN XY: 71776

African (AFR) AF: 0.158 AC: 6220 AN: 39426

American (AMR) AF: 0.508 AC: 7554 AN: 14866

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1521 AN: 3404

East Asian (EAS) AF: 0.394 AC: 1996 AN: 5066

South Asian (SAS) AF: 0.581 AC: 2700 AN: 4648

European-Finnish (FIN) AF: 0.633 AC: 6070 AN: 9588

Middle Eastern (MID) AF: 0.455 AC: 132 AN: 290

European-Non Finnish (NFE) AF: 0.553 AC: 36988 AN: 66922

Other (OTH) AF: 0.450 AC: 926 AN: 2060

Alfa AF: 0.504 Hom.: 12185

Bravo AF: 0.404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.39
PhyloP100		-0.16
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: rs2037755; hg19: chr2-224883305;