2-223981676-C-T

Variant names:

• chr2-223981676-C-T
• rs17195216
• NM_001136528.2:c.985+1005G>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.985+1005G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,076 control chromosomes in the GnomAD database, including 6,650 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 0.26 (6650 hom., cov: 33)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.771
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.985+1005G>A		intron_variant	Intron 6 of 8	ENST00000409304.6	NP_001130000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINE2	ENST00000409304.6	c.985+1005G>A		intron_variant	Intron 6 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40259 AN: 151950 Hom.: 6654 Cov.: 33

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

African (AFR) AC: 0 AN: 0

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: 0.167 AC: 1 AN: 6

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

GnomAD4 genome AF: 0.265 AC: 40254 AN: 152068 Hom.: 6650 Cov.: 33 AF XY: 0.269 AC XY: 20017 AN XY: 74308

African (AFR) AF: 0.0650 AC: 2698 AN: 41522

American (AMR) AF: 0.300 AC: 4583 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1145 AN: 5172

South Asian (SAS) AF: 0.407 AC: 1961 AN: 4818

European-Finnish (FIN) AF: 0.433 AC: 4562 AN: 10540

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.350 AC: 23800 AN: 67946

Other (OTH) AF: 0.254 AC: 535 AN: 2108

Alfa AF: 0.244 Hom.: 3149

Bravo AF: 0.242

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-0.77
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: rs17195216; hg19: chr2-224846393;