NM_001136528.2:c.550G>A

Variant names:

• chr2-223991938-C-T
• rs201689138
• NM_001136528.2:c.550G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001136528.2(SERPINE2):​c.550G>A​(p.Val184Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000127 in 1,613,148 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: SERPINE2 NM_001136528.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76
• Publications: 5 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 19 AD gene.

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.550G>A	p.Val184Ile	missense	Exon 4 of 9	NP_001130000.1	P07093-2
	SERPINE2	NM_001136530.1		c.586G>A	p.Val196Ile	missense	Exon 4 of 9	NP_001130002.1	P07093-3
	SERPINE2	NM_006216.4		c.550G>A	p.Val184Ile	missense	Exon 4 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.550G>A	p.Val184Ile	missense	Exon 4 of 9	ENSP00000386412.1	P07093-2
	SERPINE2	ENST00000258405.9	TSL:1	c.550G>A	p.Val184Ile	missense	Exon 4 of 9	ENSP00000258405.4	P07093-1
	SERPINE2	ENST00000409840.7	TSL:1	c.550G>A	p.Val184Ile	missense	Exon 5 of 10	ENSP00000386969.3	P07093-2

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000212 AC: 53 AN: 250136 AF XY: 0.000207

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000407

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000127 AC: 186 AN: 1461000 Hom.: 0 Cov.: 31 AF XY: 0.000136 AC XY: 99 AN XY: 726796

African (AFR) AF: 0.000209 AC: 7 AN: 33438

American (AMR) AF: 0.0000224 AC: 1 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26044

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86090

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000142 AC: 158 AN: 1111654

Other (OTH) AF: 0.0000994 AC: 6 AN: 60364

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74326

African (AFR) AF: 0.0000966 AC: 4 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68040

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000155 Hom.: 0

Bravo AF: 0.000110

ExAC AF: 0.000362 AC: 44

EpiCase AF: 0.000273

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Uncertain	0.42	D
MutationAssessor	Benign	1.4	L
PhyloP100		3.8
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.62	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.044	D
Polyphen		0.99	D
Vest4		0.20
MVP		0.59
MPC		0.39
ClinPred		0.10	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.51
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201689138; hg19: chr2-224856655; COSMIC: COSV51460192;