2-223992549-A-C

Position:

• chr2-223992549-A-C

Variant summary

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

The NM_001136528.2(SERPINE2):​c.488-549T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 151,926 control chromosomes in the GnomAD database, including 29,703 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 0.62 (29703 hom., cov: 31)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERPINE2	NM_001136528.2	c.488-549T>G		intron_variant		ENST00000409304.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERPINE2	ENST00000409304.6	c.488-549T>G		intron_variant		1	NM_001136528.2	A1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94225 AN: 151808 Hom.: 29687 Cov.: 31

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.621 AC: 94275 AN: 151926 Hom.: 29703 Cov.: 31 AF XY: 0.618 AC XY: 45875 AN XY: 74248

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.715

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.624

Alfa AF: 0.655 Hom.: 65732

Bravo AF: 0.625

Asia WGS AF: 0.480 AC: 1668 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.80

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: rs10191694; hg19: chr2-224857266;