2-224012844-T-G

Variant names:

• chr2-224012844-T-G
• rs7563931
• NM_001136528.2:c.-22-10922A>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.-22-10922A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,052 control chromosomes in the GnomAD database, including 49,733 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 0.80 (49733 hom., cov: 32)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.-22-10922A>C		intron_variant	Intron 1 of 8	ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.-22-10922A>C		intron_variant	Intron 1 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121512 AN: 151934 Hom.: 49739 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.799 AC: 121543 AN: 152052 Hom.: 49733 Cov.: 32 AF XY: 0.796 AC XY: 59164 AN XY: 74348

African (AFR) AF: 0.635 AC: 26310 AN: 41416

American (AMR) AF: 0.809 AC: 12359 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2967 AN: 3472

East Asian (EAS) AF: 0.576 AC: 2971 AN: 5162

South Asian (SAS) AF: 0.781 AC: 3759 AN: 4812

European-Finnish (FIN) AF: 0.873 AC: 9235 AN: 10580

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.901 AC: 61282 AN: 68012

Other (OTH) AF: 0.818 AC: 1728 AN: 2112

Alfa AF: 0.867 Hom.: 105954

Bravo AF: 0.786

Asia WGS AF: 0.655 AC: 2277 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.68
PhyloP100		0.43
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: rs7563931; hg19: chr2-224877561;