2-224033710-A-G

Variant summary

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

The NM_001136528.2(SERPINE2):c.-23+5389T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 150,268 control chromosomes in the GnomAD database, including 31,956 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 0.65 (31956 hom., cov: 26)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.869

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE2	NM_001136528.2	c.-23+5389T>C		intron_variant		ENST00000409304.6
SERPINE2	NM_001136530.1	c.14+4780T>C		intron_variant
SERPINE2	NM_006216.4	c.-23+5389T>C		intron_variant
SERPINE2	XM_005246641.3	c.14+4780T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE2	ENST00000409304.6	c.-23+5389T>C		intron_variant		1	NM_001136528.2	A1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 97673 AN: 150154 Hom.: 31934 Cov.: 26

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.657

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.650 AC: 97743 AN: 150268 Hom.: 31956 Cov.: 26 AF XY: 0.656 AC XY: 47987 AN XY: 73196

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.635

Alfa AF: 0.577 Hom.: 1838

Bravo AF: 0.649

Asia WGS AF: 0.628 AC: 2182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.9
Dann	Benign	0.71

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: rs7562213; hg19: chr2-224898427;