chr2-223982551-T-C

Variant names:

• chr2-223982551-T-C
• rs10164837
• NM_001136528.2:c.985+130A>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.985+130A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 490,612 control chromosomes in the GnomAD database, including 15,980 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 0.22 (4197 hom., cov: 33)
  • Exomes 𝑓: 0.25 (11783 hom.)
• Consequence: SERPINE2 NM_001136528.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINE2	NM_001136528.2	c.985+130A>G		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+130A>G		intron_variant	Intron 6 of 8	1	NM_001136528.2	ENSP00000386412.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32869 AN: 152082 Hom.: 4201 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.248 AC: 83920 AN: 338412 Hom.: 11783 Cov.: 5 AF XY: 0.246 AC XY: 43484 AN XY: 176866

African (AFR) AF: 0.0946 AC: 807 AN: 8528

American (AMR) AF: 0.162 AC: 1653 AN: 10174

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 2794 AN: 10804

East Asian (EAS) AF: 0.0470 AC: 1167 AN: 24820

South Asian (SAS) AF: 0.139 AC: 3066 AN: 22096

European-Finnish (FIN) AF: 0.231 AC: 6822 AN: 29492

Middle Eastern (MID) AF: 0.223 AC: 347 AN: 1554

European-Non Finnish (NFE) AF: 0.296 AC: 62457 AN: 210678

Other (OTH) AF: 0.237 AC: 4807 AN: 20266

GnomAD4 genome AF: 0.216 AC: 32863 AN: 152200 Hom.: 4197 Cov.: 33 AF XY: 0.209 AC XY: 15582 AN XY: 74406

African (AFR) AF: 0.107 AC: 4425 AN: 41534

American (AMR) AF: 0.186 AC: 2844 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 951 AN: 3466

East Asian (EAS) AF: 0.0175 AC: 91 AN: 5188

South Asian (SAS) AF: 0.141 AC: 680 AN: 4824

European-Finnish (FIN) AF: 0.223 AC: 2363 AN: 10584

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.302 AC: 20538 AN: 67982

Other (OTH) AF: 0.223 AC: 471 AN: 2116

Alfa AF: 0.263 Hom.: 10039

Bravo AF: 0.211

Asia WGS AF: 0.0920 AC: 323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.19
DANN	Benign	0.39
PhyloP100		-0.089
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: rs10164837; hg19: chr2-224847268;