chr2-223983089-C-T

Variant names:

• chr2-223983089-C-T
• rs7605945
• NM_001136528.2:c.885-308G>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.885-308G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,080 control chromosomes in the GnomAD database, including 32,948 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 0.63 (32948 hom., cov: 32)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.783 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.885-308G>A		intron	N/A	NP_001130000.1
	SERPINE2	NM_001136530.1		c.921-308G>A		intron	N/A	NP_001130002.1
	SERPINE2	NM_006216.4		c.885-308G>A		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.885-308G>A		intron	N/A	ENSP00000386412.1
	SERPINE2	ENST00000258405.9	TSL:1	c.885-308G>A		intron	N/A	ENSP00000258405.4
	SERPINE2	ENST00000409840.7	TSL:1	c.885-308G>A		intron	N/A	ENSP00000386969.3

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95931 AN: 151962 Hom.: 32943 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.625

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.631 AC: 95971 AN: 152080 Hom.: 32948 Cov.: 32 AF XY: 0.627 AC XY: 46624 AN XY: 74356

African (AFR) AF: 0.383 AC: 15860 AN: 41450

American (AMR) AF: 0.609 AC: 9305 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2243 AN: 3470

East Asian (EAS) AF: 0.264 AC: 1364 AN: 5166

South Asian (SAS) AF: 0.615 AC: 2957 AN: 4806

European-Finnish (FIN) AF: 0.784 AC: 8300 AN: 10588

Middle Eastern (MID) AF: 0.610 AC: 177 AN: 290

European-Non Finnish (NFE) AF: 0.789 AC: 53631 AN: 68008

Other (OTH) AF: 0.632 AC: 1331 AN: 2106

Alfa AF: 0.724 Hom.: 153237

Bravo AF: 0.606

Asia WGS AF: 0.441 AC: 1537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0030
DANN	Benign	0.66
PhyloP100		-1.2
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: rs7605945; hg19: chr2-224847806;