2-224020589-T-G

Variant names:

• chr2-224020589-T-G
• rs2099601
• NM_001136528.2:c.-23+18510A>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.-23+18510A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.945 in 152,188 control chromosomes in the GnomAD database, including 68,264 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 0.94 (68264 hom., cov: 31)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• Publications: 0 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]

ENSG00000310283 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.987 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE2	NM_001136528.2	MANE Select	c.-23+18510A>C		intron	N/A	NP_001130000.1	P07093-2
	SERPINE2	NM_001136530.1		c.14+17901A>C		intron	N/A	NP_001130002.1	P07093-3
	SERPINE2	NM_006216.4		c.-23+18510A>C		intron	N/A	NP_006207.1	P07093-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE2	ENST00000409304.6	TSL:1 MANE Select	c.-23+18510A>C		intron	N/A	ENSP00000386412.1	P07093-2
	SERPINE2	ENST00000258405.9	TSL:1	c.-23+18510A>C		intron	N/A	ENSP00000258405.4	P07093-1
	SERPINE2	ENST00000409840.7	TSL:1	c.-23+9483A>C		intron	N/A	ENSP00000386969.3	P07093-2

Frequencies

GnomAD3 genomes AF: 0.945 AC: 143680 AN: 152070 Hom.: 68232 Cov.: 31

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.945 AC: 143768 AN: 152188 Hom.: 68264 Cov.: 31 AF XY: 0.944 AC XY: 70274 AN XY: 74410

African (AFR) AF: 0.858 AC: 35578 AN: 41470

American (AMR) AF: 0.970 AC: 14850 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3432 AN: 3472

East Asian (EAS) AF: 0.781 AC: 4037 AN: 5166

South Asian (SAS) AF: 0.937 AC: 4521 AN: 4826

European-Finnish (FIN) AF: 0.997 AC: 10579 AN: 10610

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

European-Non Finnish (NFE) AF: 0.994 AC: 67583 AN: 68024

Other (OTH) AF: 0.949 AC: 2000 AN: 2108

Alfa AF: 0.986 Hom.: 9309

Bravo AF: 0.937

Asia WGS AF: 0.818 AC: 2848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.2
DANN	Benign	0.57
PhyloP100		-0.33
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: rs2099601; hg19: chr2-224885306;