2-223982990-T-C

Variant names:

• chr2-223982990-T-C
• rs975278
• NM_001136528.2:c.885-209A>G

Variant summary

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

The NM_001136528.2(SERPINE2):​c.885-209A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,182 control chromosomes in the GnomAD database, including 45,282 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 (45282 hom., cov: 33)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• Publications: 21 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.885-209A>G		intron_variant	Intron 5 of 8	ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.885-209A>G		intron_variant	Intron 5 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116616 AN: 152064 Hom.: 45255 Cov.: 33

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.767 AC: 116697 AN: 152182 Hom.: 45282 Cov.: 33 AF XY: 0.763 AC XY: 56726 AN XY: 74386

African (AFR) AF: 0.714 AC: 29639 AN: 41494

American (AMR) AF: 0.807 AC: 12352 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2467 AN: 3470

East Asian (EAS) AF: 0.444 AC: 2300 AN: 5178

South Asian (SAS) AF: 0.671 AC: 3238 AN: 4826

European-Finnish (FIN) AF: 0.790 AC: 8364 AN: 10592

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

European-Non Finnish (NFE) AF: 0.819 AC: 55712 AN: 68002

Other (OTH) AF: 0.757 AC: 1601 AN: 2114

Alfa AF: 0.796 Hom.: 197572

Bravo AF: 0.768

Asia WGS AF: 0.553 AC: 1925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.9
DANN	Benign	0.43
PhyloP100		-0.036
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: rs975278; hg19: chr2-224847707;