chr2-224033710-A-G

Variant names:

• chr2-224033710-A-G
• rs7562213
• NM_001136528.2:c.-23+5389T>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+5389T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 150,268 control chromosomes in the GnomAD database, including 31,956 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 0.65 (31956 hom., cov: 26)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.869
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.691 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.-23+5389T>C		intron	N/A	NP_001130000.1
	SERPINE2	NM_001136530.1		c.14+4780T>C		intron	N/A	NP_001130002.1
	SERPINE2	NM_006216.4		c.-23+5389T>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.-23+5389T>C		intron	N/A	ENSP00000386412.1
	SERPINE2	ENST00000258405.9	TSL:1	c.-23+5389T>C		intron	N/A	ENSP00000258405.4
	SERPINE2	ENST00000447280.6	TSL:2	c.14+4780T>C		intron	N/A	ENSP00000415786.2

Frequencies

GnomAD3 genomes AF: 0.650 AC: 97673 AN: 150154 Hom.: 31934 Cov.: 26

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.657

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.650 AC: 97743 AN: 150268 Hom.: 31956 Cov.: 26 AF XY: 0.656 AC XY: 47987 AN XY: 73196

African (AFR) AF: 0.612 AC: 24985 AN: 40810

American (AMR) AF: 0.702 AC: 10610 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2290 AN: 3460

East Asian (EAS) AF: 0.590 AC: 3016 AN: 5110

South Asian (SAS) AF: 0.710 AC: 3378 AN: 4756

European-Finnish (FIN) AF: 0.721 AC: 7194 AN: 9978

Middle Eastern (MID) AF: 0.655 AC: 190 AN: 290

European-Non Finnish (NFE) AF: 0.652 AC: 44171 AN: 67768

Other (OTH) AF: 0.635 AC: 1323 AN: 2084

Alfa AF: 0.577 Hom.: 1838

Bravo AF: 0.649

Asia WGS AF: 0.628 AC: 2182 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	4.9
DANN	Benign	0.71
PhyloP100		0.87
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: rs7562213; hg19: chr2-224898427;