2-223977317-C-T

Position:

• chr2-223977317-C-T

Variant summary

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

The NM_001136528.2(SERPINE2):​c.1156+227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0539 in 152,200 control chromosomes in the GnomAD database, including 389 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 0.054 (389 hom., cov: 33)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.1156+227G>A		intron_variant		ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.1156+227G>A		intron_variant		1	NM_001136528.2	ENSP00000386412	A1

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 8193 AN: 152082 Hom.: 387 Cov.: 33

Gnomad AFR AF: 0.0726

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0426

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.0535

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

GnomAD4 genome AF: 0.0539 AC: 8209 AN: 152200 Hom.: 389 Cov.: 33 AF XY: 0.0567 AC XY: 4219 AN XY: 74424

Gnomad4 AFR AF: 0.0725

Gnomad4 AMR AF: 0.0454

Gnomad4 ASJ AF: 0.0686

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.0426

Gnomad4 NFE AF: 0.0277

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0434 Hom.: 19

Bravo AF: 0.0534

Asia WGS AF: 0.174 AC: 604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.66
DANN	Benign	0.69

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: rs35742624; hg19: chr2-224842034;