chr2-223994033-T-C

Variant names:

• chr2-223994033-T-C
• rs6738983
• NM_001136528.2:c.488-2033A>G

Variant summary

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

The NM_001136528.2(SERPINE2):​c.488-2033A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,052 control chromosomes in the GnomAD database, including 23,636 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 0.53 (23636 hom., cov: 31)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688
• Publications: 10 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.488-2033A>G		intron_variant	Intron 3 of 8	ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.488-2033A>G		intron_variant	Intron 3 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80087 AN: 151932 Hom.: 23645 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.527 AC: 80086 AN: 152052 Hom.: 23636 Cov.: 31 AF XY: 0.524 AC XY: 38951 AN XY: 74328

African (AFR) AF: 0.264 AC: 10939 AN: 41468

American (AMR) AF: 0.537 AC: 8196 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1626 AN: 3472

East Asian (EAS) AF: 0.275 AC: 1424 AN: 5174

South Asian (SAS) AF: 0.558 AC: 2686 AN: 4816

European-Finnish (FIN) AF: 0.669 AC: 7083 AN: 10584

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46272 AN: 67962

Other (OTH) AF: 0.533 AC: 1126 AN: 2114

Alfa AF: 0.627 Hom.: 67719

Bravo AF: 0.504

Asia WGS AF: 0.402 AC: 1401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.56
DANN	Benign	0.51
PhyloP100		-0.69
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: rs6738983; hg19: chr2-224858750;