rs2099603

Variant names:

• chr2-223987964-C-T
• rs2099603
• NM_001136528.2:c.686-3014G>A

Variant summary

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

The NM_001136528.2(SERPINE2):​c.686-3014G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.978 in 152,308 control chromosomes in the GnomAD database, including 72,940 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 0.98 (72940 hom., cov: 32)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.686-3014G>A		intron_variant	Intron 4 of 8	ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.686-3014G>A		intron_variant	Intron 4 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.978 AC: 148879 AN: 152190 Hom.: 72888 Cov.: 32

Gnomad AFR AF: 0.996

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.987

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.967

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

GnomAD4 genome AF: 0.978 AC: 148986 AN: 152308 Hom.: 72940 Cov.: 32 AF XY: 0.975 AC XY: 72587 AN XY: 74470

African (AFR) AF: 0.996 AC: 41391 AN: 41558

American (AMR) AF: 0.987 AC: 15113 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3394 AN: 3470

East Asian (EAS) AF: 0.834 AC: 4316 AN: 5178

South Asian (SAS) AF: 0.975 AC: 4706 AN: 4828

European-Finnish (FIN) AF: 0.931 AC: 9875 AN: 10610

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.985 AC: 67005 AN: 68042

Other (OTH) AF: 0.962 AC: 2031 AN: 2112

Alfa AF: 0.977 Hom.: 20948

Bravo AF: 0.981

Asia WGS AF: 0.871 AC: 3029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.38
PhyloP100		-0.51
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: rs2099603; hg19: chr2-224852681;