2-224013584-A-G

Position:

• chr2-224013584-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136528.2(SERPINE2):​c.-22-11662T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,108 control chromosomes in the GnomAD database, including 1,286 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 (1286 hom., cov: 32)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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]

LOC124907990 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE2	NM_001136528.2	c.-22-11662T>C		intron_variant		ENST00000409304.6
LOC124907990	XR_007088102.1	n.281+4427A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE2	ENST00000409304.6	c.-22-11662T>C		intron_variant		1	NM_001136528.2	A1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18686 AN: 151990 Hom.: 1280 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0860

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.123 AC: 18731 AN: 152108 Hom.: 1286 Cov.: 32 AF XY: 0.126 AC XY: 9398 AN XY: 74382

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0860

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0962 Hom.: 771

Bravo AF: 0.125

Asia WGS AF: 0.155 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs1438828; hg19: chr2-224878301;