2-223974979-T-C

Variant names:

• chr2-223974979-T-C
• rs6754561
• NM_001136528.2:c.*888A>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.*888A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,042 control chromosomes in the GnomAD database, including 14,093 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 0.42 (14093 hom., cov: 32)
  • Exomes 𝑓: 0.30 (0 hom.)
• Consequence: SERPINE2 NM_001136528.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.990
• Publications: 9 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 (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.*888A>G		downstream_gene_variant		ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.*888A>G		downstream_gene_variant		1	NM_001136528.2	ENSP00000386412.1
SERPINE2	ENST00000258405.9	c.*888A>G		downstream_gene_variant		1		ENSP00000258405.4
SERPINE2	ENST00000409840.7	c.*888A>G		downstream_gene_variant		1		ENSP00000386969.3
SERPINE2	ENST00000473202.1	n.*174A>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.421 AC: 64007 AN: 151914 Hom.: 14071 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.415

GnomAD4 exome AF: 0.300 AC: 3 AN: 10 Hom.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 2 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.422 AC: 64083 AN: 152032 Hom.: 14093 Cov.: 32 AF XY: 0.417 AC XY: 30974 AN XY: 74300

African (AFR) AF: 0.561 AC: 23240 AN: 41462

American (AMR) AF: 0.439 AC: 6710 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1435 AN: 3472

East Asian (EAS) AF: 0.411 AC: 2123 AN: 5162

South Asian (SAS) AF: 0.346 AC: 1668 AN: 4824

European-Finnish (FIN) AF: 0.271 AC: 2856 AN: 10556

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.362 AC: 24615 AN: 67964

Other (OTH) AF: 0.417 AC: 878 AN: 2108

Alfa AF: 0.383 Hom.: 48734

Bravo AF: 0.444

Asia WGS AF: 0.384 AC: 1335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.095
DANN	Benign	0.22
PhyloP100		-0.99

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6754561; hg19: chr2-224839696;