2-223986006-G-C

Variant names:

• chr2-223986006-G-C
• rs6748795
• NM_001136528.2:c.686-1056C>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.686-1056C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,042 control chromosomes in the GnomAD database, including 33,942 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 0.65 (33942 hom., cov: 32)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136528.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE2	NM_001136528.2	MANE Select	c.686-1056C>G		intron	N/A	NP_001130000.1
	SERPINE2	NM_001136530.1		c.722-1056C>G		intron	N/A	NP_001130002.1
	SERPINE2	NM_006216.4		c.686-1056C>G		intron	N/A	NP_006207.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE2	ENST00000409304.6	TSL:1 MANE Select	c.686-1056C>G		intron	N/A	ENSP00000386412.1
	SERPINE2	ENST00000258405.9	TSL:1	c.686-1056C>G		intron	N/A	ENSP00000258405.4
	SERPINE2	ENST00000409840.7	TSL:1	c.686-1056C>G		intron	N/A	ENSP00000386969.3

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98168 AN: 151924 Hom.: 33935 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.646 AC: 98213 AN: 152042 Hom.: 33942 Cov.: 32 AF XY: 0.642 AC XY: 47678 AN XY: 74312

African (AFR) AF: 0.431 AC: 17863 AN: 41448

American (AMR) AF: 0.616 AC: 9406 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2242 AN: 3472

East Asian (EAS) AF: 0.264 AC: 1361 AN: 5154

South Asian (SAS) AF: 0.614 AC: 2949 AN: 4800

European-Finnish (FIN) AF: 0.784 AC: 8301 AN: 10588

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53753 AN: 67996

Other (OTH) AF: 0.642 AC: 1357 AN: 2114

Alfa AF: 0.654 Hom.: 2187

Bravo AF: 0.623

Asia WGS AF: 0.441 AC: 1539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1
DANN	Benign	0.62
PhyloP100		0.23
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: rs6748795; hg19: chr2-224850723;