2-224004926-G-C

Position:

• chr2-224004926-G-C

Variant summary

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

The NM_001136528.2(SERPINE2):​c.-22-3004C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 147,788 control chromosomes in the GnomAD database, including 34,957 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 0.68 (34957 hom., cov: 26)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE2	NM_001136528.2	c.-22-3004C>G		intron_variant		ENST00000409304.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE2	ENST00000409304.6	c.-22-3004C>G		intron_variant		1	NM_001136528.2	A1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 100906 AN: 147732 Hom.: 34972 Cov.: 26

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.683 AC: 100900 AN: 147788 Hom.: 34957 Cov.: 26 AF XY: 0.685 AC XY: 49244 AN XY: 71880

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.697

Alfa AF: 0.690 Hom.: 4336

Bravo AF: 0.670

Asia WGS AF: 0.616 AC: 2137 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.023
DANN	Benign	0.18

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: rs2118409; hg19: chr2-224869643;