2-224001460-A-G

Variant names:

• chr2-224001460-A-G
• rs3795877
• NM_001136528.2:c.259+182T>C

Variant summary

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

The NM_001136528.2(SERPINE2):​c.259+182T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 608,154 control chromosomes in the GnomAD database, including 16,196 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 0.26 (6309 hom., cov: 32)
  • Exomes 𝑓: 0.20 (9887 hom.)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE2	NM_001136528.2	MANE Select	c.259+182T>C		intron	N/A	NP_001130000.1
	SERPINE2	NM_001136530.1		c.295+182T>C		intron	N/A	NP_001130002.1
	SERPINE2	NM_006216.4		c.259+182T>C		intron	N/A	NP_006207.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE2	ENST00000409304.6	TSL:1 MANE Select	c.259+182T>C		intron	N/A	ENSP00000386412.1
	SERPINE2	ENST00000258405.9	TSL:1	c.259+182T>C		intron	N/A	ENSP00000258405.4
	SERPINE2	ENST00000409840.7	TSL:1	c.259+182T>C		intron	N/A	ENSP00000386969.3

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39703 AN: 152014 Hom.: 6298 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.199 AC: 90600 AN: 456022 Hom.: 9887 AF XY: 0.198 AC XY: 46693 AN XY: 236372

African (AFR) AF: 0.451 AC: 5510 AN: 12204

American (AMR) AF: 0.178 AC: 2812 AN: 15808

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 2897 AN: 12732

East Asian (EAS) AF: 0.161 AC: 4694 AN: 29146

South Asian (SAS) AF: 0.169 AC: 6005 AN: 35584

European-Finnish (FIN) AF: 0.116 AC: 3190 AN: 27488

Middle Eastern (MID) AF: 0.294 AC: 540 AN: 1838

European-Non Finnish (NFE) AF: 0.201 AC: 59392 AN: 295960

Other (OTH) AF: 0.220 AC: 5560 AN: 25262

GnomAD4 genome AF: 0.261 AC: 39747 AN: 152132 Hom.: 6309 Cov.: 32 AF XY: 0.256 AC XY: 19020 AN XY: 74398

African (AFR) AF: 0.451 AC: 18685 AN: 41458

American (AMR) AF: 0.212 AC: 3247 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 795 AN: 3470

East Asian (EAS) AF: 0.141 AC: 730 AN: 5166

South Asian (SAS) AF: 0.165 AC: 797 AN: 4826

European-Finnish (FIN) AF: 0.111 AC: 1173 AN: 10608

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13501 AN: 67990

Other (OTH) AF: 0.257 AC: 544 AN: 2116

Alfa AF: 0.222 Hom.: 2313

Bravo AF: 0.280

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.77
PhyloP100		-0.21
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: rs3795877; hg19: chr2-224866177;