chr2-224018986-C-T

Variant names:

• chr2-224018986-C-T
• rs1438829
• NM_001136528.2:c.-22-17064G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136528.2(SERPINE2):​c.-22-17064G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.945 in 152,260 control chromosomes in the GnomAD database, including 68,285 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 0.94 (68285 hom., cov: 32)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 0 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]

LOC124907990 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.-22-17064G>A		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.-22-17064G>A		intron_variant	Intron 1 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.945 AC: 143739 AN: 152142 Hom.: 68253 Cov.: 32

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.945 AC: 143827 AN: 152260 Hom.: 68285 Cov.: 32 AF XY: 0.945 AC XY: 70324 AN XY: 74452

African (AFR) AF: 0.858 AC: 35624 AN: 41536

American (AMR) AF: 0.970 AC: 14848 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3432 AN: 3472

East Asian (EAS) AF: 0.782 AC: 4028 AN: 5152

South Asian (SAS) AF: 0.937 AC: 4514 AN: 4816

European-Finnish (FIN) AF: 0.997 AC: 10591 AN: 10622

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67594 AN: 68038

Other (OTH) AF: 0.949 AC: 2008 AN: 2116

Alfa AF: 0.970 Hom.: 8902

Bravo AF: 0.937

Asia WGS AF: 0.819 AC: 2851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.18
DANN	Benign	0.30
PhyloP100		-1.6
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: rs1438829; hg19: chr2-224883703;