2-223984765-C-T

Variant names:

• chr2-223984765-C-T
• rs186094760
• NM_001136528.2:c.871G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001136528.2(SERPINE2):​c.871G>A​(p.Val291Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V291L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERPINE2 NM_001136528.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39
• Publications: 2 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE2	NM_001136528.2	MANE Select	c.871G>A	p.Val291Met	missense	Exon 5 of 9	NP_001130000.1	P07093-2
	SERPINE2	NM_001136530.1		c.907G>A	p.Val303Met	missense	Exon 5 of 9	NP_001130002.1	P07093-3
	SERPINE2	NM_006216.4		c.871G>A	p.Val291Met	missense	Exon 5 of 9	NP_006207.1	P07093-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERPINE2	ENST00000409304.6	TSL:1 MANE Select	c.871G>A	p.Val291Met	missense	Exon 5 of 9	ENSP00000386412.1	P07093-2
	SERPINE2	ENST00000258405.9	TSL:1	c.871G>A	p.Val291Met	missense	Exon 5 of 9	ENSP00000258405.4	P07093-1
	SERPINE2	ENST00000409840.7	TSL:1	c.871G>A	p.Val291Met	missense	Exon 6 of 10	ENSP00000386969.3	P07093-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Pathogenic	0.96	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		2.4
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.63
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.036	D
Polyphen		0.96	D
Vest4		0.56
MutPred		0.64		Gain of MoRF binding (P = 0.0737)
MVP		0.74
MPC		0.91
ClinPred		0.87	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.65
Mutation Taster		=81/19	polymorphism

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: rs186094760; hg19: chr2-224849482;