2-223997983-C-A

Variant names:

• chr2-223997983-C-A
• rs36034130
• NM_001136528.2:c.487+132G>T

Variant summary

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

The NM_001136528.2(SERPINE2):​c.487+132G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 691,978 control chromosomes in the GnomAD database, including 4,593 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 (1326 hom., cov: 32)
  • Exomes 𝑓: 0.10 (3267 hom.)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.487+132G>T		intron_variant	Intron 3 of 8	ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.487+132G>T		intron_variant	Intron 3 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18559 AN: 152070 Hom.: 1321 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0932

Gnomad OTH AF: 0.0896

GnomAD4 exome AF: 0.102 AC: 54996 AN: 539790 Hom.: 3267 AF XY: 0.105 AC XY: 30070 AN XY: 285748

African (AFR) AF: 0.175 AC: 2577 AN: 14748

American (AMR) AF: 0.142 AC: 3968 AN: 27850

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 1934 AN: 15974

East Asian (EAS) AF: 0.0189 AC: 607 AN: 32078

South Asian (SAS) AF: 0.163 AC: 8487 AN: 52164

European-Finnish (FIN) AF: 0.113 AC: 3946 AN: 34918

Middle Eastern (MID) AF: 0.0810 AC: 310 AN: 3828

European-Non Finnish (NFE) AF: 0.0921 AC: 30268 AN: 328622

Other (OTH) AF: 0.0979 AC: 2899 AN: 29608

GnomAD4 genome AF: 0.122 AC: 18597 AN: 152188 Hom.: 1326 Cov.: 32 AF XY: 0.123 AC XY: 9169 AN XY: 74422

African (AFR) AF: 0.177 AC: 7363 AN: 41524

American (AMR) AF: 0.127 AC: 1944 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 441 AN: 3472

East Asian (EAS) AF: 0.0235 AC: 122 AN: 5186

South Asian (SAS) AF: 0.162 AC: 782 AN: 4824

European-Finnish (FIN) AF: 0.112 AC: 1186 AN: 10592

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0932 AC: 6337 AN: 67988

Other (OTH) AF: 0.0882 AC: 186 AN: 2110

Alfa AF: 0.0771 Hom.: 141

Bravo AF: 0.124

Asia WGS AF: 0.0810 AC: 284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.17
DANN	Benign	0.68
PhyloP100		-1.5
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: rs36034130; hg19: chr2-224862700;